Journal name: Patient Preference and Adherence
`Article Designation: Review
`Year: 2016
`Volume: 10
`Running head verso: Li
`Running head recto: Utility of C1 esterase inhibitor concentrates for HAE
`DOI: http://dx.doi.org/10.2147/PPA.S86379
`
`Patient Preference and Adherence
`
`Open Access Full Text Article
`
`Dovepress
`
`open access to scientific and medical research
`
`R e v i e w
`
`Self-administered C1 esterase inhibitor
`concentrates for the management of hereditary
`angioedema: usability and patient acceptance
`
`Huamin Henry Li
`institute for Asthma and Allergy,
`Chevy Chase, MD, USA
`
`Correspondence: Huamin Henry Li
`institute for Asthma and Allergy,
`2 wisconsin Circle, Suite 250, Chevy
`Chase, MD 20815, USA
`Tel +1 301 986 9262
`Fax +1 301 907 7910
`email hl@allergyasthma.us
`
`Abstract: Hereditary angioedema (HAE) is a rare genetic disease characterized by episodic
`subcutaneous or submucosal swelling. The primary cause for the most common form of HAE
`is a deficiency in functional C1 esterase inhibitor (C1-INH). The swelling caused by HAE can
`be painful, disfiguring, and life-threatening. It reduces daily function and compromises the
`quality of life of affected individuals and their caregivers. Among different treatment strategies,
`replacement with C1-INH concentrates is employed for on-demand treatment of acute attacks
`and long-term prophylaxis. Three human plasma-derived C1-INH preparations are approved
`for HAE treatment in the US, the European Union, or both regions: Cinryze®, Berinert®, and
`Cetor®; however, only Cinryze is approved for long-term prophylaxis. Postmarketing studies
`have shown that home therapy (self-administered or administered by a caregiver) is a conve-
`nient and safe option preferred by many HAE patients. In this review, we summarize the role
`of self-administered plasma-derived C1-INH concentrate therapy with Cinryze at home in the
`prophylaxis of HAE.
`Keywords: C1-INH concentrate, hereditary angioedema, disease management, first line,
`prophylaxis, self-administration
`
`Introduction
`Hereditary angioedema (HAE) due to C1 esterase inhibitor (C1-INH) deficiency is a
`rare autosomal dominant disorder characterized by episodic swelling typically involv-
`ing the skin, abdomen, and larynx.1,2 Studies suggest that HAE affects up to one in
`50,000 people worldwide, regardless of race or ethnicity.3–5 The majority of HAE
`cases are due to the deficiency of functional C1-INH. HAE due to C1-INH deficiency
`is further divided into HAE types I and II, and the presentations of these subtypes are
`clinically indistinguishable. There are ~300 identified mutations of the C1-INH gene
`(SERPING1) located at 11q12–q13.1 related to HAE.6
`HAE type I accounts for 85% of cases. Patients with this form of HAE have low-
`level production of antigenic C1-INH. These patients have normal antigenic levels
`but abnormal C1-INH function.7,8 Under physiological conditions, C1-INH regulates
`the activities of four interlinked proteolytic enzyme cascades, namely, the comple-
`ment, contact (kallikrein–kinin), fibrinolytic, and coagulation pathways (Figure 1). In
`particular, C1-INH is the primary inhibitor of the kallikrein–kinin system via inactiva-
`tion of activated factor XII (factor XIIa) and kallikrein. The excessive production of
`bradykinin via an overactive kallikrein–kinin system accounts for episodic swelling
`in patients with HAE.4,9,10
`
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`1727
`Patient Preference and Adherence 2016:10 1727–1737
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`Figure 1 Pathways inhibited by C1-iNH.
`Notes: Horizontal bars over the complement names indicate activation. Copyright © 2014. Future Medicine Ltd. Reproduced from Bork K. Pasteurized and nanofiltered,
`plasma-derived C1 esterase inhibitor concentrate for the treatment of hereditary angioedema. Immunotherapy. 2014;6(5):533–551.11
`Abbreviations: C1-iNH, C1 esterase inhibitor; FXi, factor Xi; FXia, activated factor Xi; FXii, factor Xii; FXiia, activated factor Xii; HMwK, high molecular weight kininogen;
`MASP, mannose-binding lectin-associated serine protease; tPA/uPA, tissue/urokinase plasminogen activator.
`
`For most patients with HAE, their clinical presentation
`is often unpredictable. The mean time at which the initial
`symptoms of HAE appear is ~11 years of age. HAE attacks
`often become more frequent and severe during adolescence
`and adulthood.1,4,12 The pattern of HAE attacks may vary
`tremendously among patients and throughout a patient’s life.
`
`Many attacks may involve multiple organ systems. Patients
`can experience symptoms weekly, while others have attacks
`less than once a year.12–15
`Without treatment, most episodes of HAE last for
`2–5 days.16 Laryngeal attacks, which occur in up to 50% of
`HAE patients, are potentially life-threatening;12,17–19 without
`
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`Utility of C1 esterase inhibitor concentrates for HAe
`
`Abbreviations: C1-iNH, C1 esterase inhibitor; eU, european Union; FDA, US Food and Drug Administration; HAe, hereditary angioedema.
`Notes: Short-term prophylaxis refers to prophylaxis before surgical or dental procedures. Long-term prophylaxis refers to routine prevention. “For acute attacks” means on-demand treatment.
`
`can be self-administered or administered at home
`in adults and adolescents only (.12 years of age);
`
`2°C–8°C; 48±10 hours
`Lyophilized and stored at
`
`1,000 U
`
`can be self-administered or administered at home
`in adults and adolescents only (.12 years of age);
`
`2°C–25°C; 48±10 hours
`Lyophilized and stored at
`
`infusion rate 1 mL/min
`1,000 U every 3–4 days;
`
`administered or administered at home
`For .12 years and ,65 years of age; can be self-
`
`Administration
`
`2°C–25°C; 32–47 hours
`Lyophilized and stored at
`half-life in adults
`Storage and plasma
`
`20 iU/kg
`
`Dosage
`
`Berinert® (CSL Behring)
`(company)
`Trade name
`Table 1 Approval status of intravenously delivered human plasma-derived C1-iNH concentrates for treatment of or prophylaxis against acute HAe attacks
`
`medical intervention, the mortality rate due to laryngeal
`edema is up to 40%.18 HAE-associated abdominal attacks
`have a high symptom burden because local mucosal swelling
`gives rise to severe abdominal pain, nausea, and vomiting,
`often necessitating hospitalization. Furthermore, unnecessary
`exploratory surgery is sometimes performed in undiagnosed
`patients.20
`The triggers for a particular attack in a patient with
`HAE are not always clear, but several factors have been
`linked to the onset of HAE attacks. The common triggers
`may include trauma, surgical and dental procedures, stress,
`infection, hormonal changes, and treatment with estrogens
`or angiotensin-converting enzyme inhibitors.21–23 Due to the
`unpredictable nature of the disease, many patients with HAE
`are constantly living in fear of another severe attack, disfig-
`ured face, impaired functions of hands and feet, agonizing
`abdominal pain, and possible airway compromise. In addi-
`tion, they worry about their children inheriting the disease.15,24
`Consequently, HAE exerts a profound humanistic burden,
`with effects including physical and emotional trauma, educa-
`tional or professional underachievement, financial hardship,
`and poor quality of life.15,24–28
`HAE treatments have been developed for short-term or
`long-term prophylaxis and for treating acute attacks.29–31
`There are a few human plasma-derived C1-INH con-
`centrates that are currently approved by the US Food
`and Drug Administration (FDA) or European Medicines
`Agency (EMA) for HAE treatment (Table 1). In line with
`the current recommendations, all HAE attacks should
`be treated.29–31 Moreover, long-term prophylaxis should
`be considered when the patient has severe and frequent
`attacks that cannot be adequately controlled by on-demand
`therapies or when rapid access to treatment of an attack
`is unavailable.29–31
`
`Prophylactic treatment with
`C1-INH concentrates
`To minimize the effect of the disease on patients, effective
`prophylaxis against HAE attacks is most desirable. The effec-
`tiveness of androgens such as danazol is limited by adverse
`events (AEs). Oral antifibrinolytics such as tranexamic acid
`have relatively poor efficacy for this rare indication.29–31 Pro-
`phylactic administration of C1-INH concentrates replenishes
`plasma C1-INH activity and thus addresses the fundamental
`cause of HAE attacks. There are three highly purified human
`plasma-derived C1-INH concentrate preparations that are
`commercially available for HAE treatment (Table 1), but
`only Cinryze® (Shire ViroPharma Incorporated, Lexington,
`MA, USA), a nanofiltered human C1-INH concentrate,
`
`Patient Preference and Adherence 2016:10
`
`FDA: not approved
`France, and Luxembourg only for acute attacks36
`eU: approved in 1997 in the Netherlands, Belgium, Finland,
`FDA: approved in October 2008 for long-term prophylaxis35
`and long-term prophylaxis34
`eU: approved in June 2011 for acute attacks, short-term,
`abdominal attacks only33
`FDA: approved in October 2009 for acute facial and
`only32
`eU: approved in April 2013 for short-term prophylaxis
`
`Approval status
`
`Cetor® (Sanquin)
`
`viroPharma incorporated)
`Cinryze® (Shire
`
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`is recommended as a first-line therapy for routine long-term
`prophylaxis (in adolescent and adult patients). Berinert®
`(CSL Behring, King of Prussia, PA, USA) is approved for
`the short-term prevention (in the EU), and Cetor® (Sanquin,
`Amsterdam, the Netherlands) has no approval for prophylac-
`tic use, although it has the same qualitative and quantitative
`composition in terms of the active substance as Cinryze.37
`Cinryze is also the only approved C1-INH concentrate for the
`treatment, preprocedure prevention, and long-term preven-
`tion of HAE attacks (in adolescents and adults) albeit only
`in the EU; in the US, its approved indication is limited to
`long-term prophylaxis.38
`Ruconest ® (Pharming Group NV, Leiden, the
`Netherlands),39,40 which is a recombinant C1-INH produced
`in transgenic rabbits, ecallantide (Kalbitor®; Dyax Corpora-
`tion, Burlington, MA, USA),41 a kallikrein inhibitor, and
`icatibant (Firazyr®; Shire, Lexington, MA, USA),42,43 a bra-
`dykinin B2 receptor antagonist, are approved treatments for
`acute HAE attacks in the US, the EU, or both. Because they
`are not plasma-derived C1-INH concentrates, these drugs
`are not discussed any further in this review.
`The objective of this review is to summarize the role
`of self-administered plasma-derived C1-INH concentrate
`therapy at home for the prevention of HAE.
`
`Clinical studies
`Plasma-derived C1-INH concentrates have performed
`well as preventative measures against HAE attacks in con-
`trolled studies, as well as in observational and descriptive
`studies.44,45
`
`total number of days with symptoms of swelling were also
`reduced.45 This study also revealed that patients with HAE
`had significantly better health-related quality of life fol-
`lowing 12 weeks of routine prophylaxis with Cinryze. This
`preventative treatment was compared with acute treatment
`of attacks without long-term prevention (patients receiving
`a placebo).47 In an open-label multicenter extension phase
`of this study, treatment with Cinryze for up to 2.6 years also
`exerted durable prophylaxis in most patients with HAE,
`with a 93.7% reduction in the median number of attacks per
`month (3.00–0.19).48
`A further study found that escalating the dose of Cinryze
`up to 2,500 U every 3 or 4 days is well tolerated and may be
`required in patients who are not responsive to the approved
`dose of 1,000 U administered at the same frequency.49
`
`Berinert
`In a retrospective study based on clinical record review,
`preprocedural Berinert administration was associated with
`a lower incidence of facial swelling or laryngeal edema after
`tooth extraction, compared with patients who did not receive
`prophylaxis. In a large-scale observational study with long-
`term follow-up, short-term prophylaxis with Berinert for
`various dental and nondental surgical procedures reduced the
`number of patients who experienced postprocedural attacks
`significantly more than tranexamic acid and danazol.50
`The data regarding the use of Berinert as a long-term
`prophylactic measure are limited. However, non-placebo-
`controlled studies showed that this preparation reduced the
`severity and number of HAE attacks.51–53
`
`Cinryze
`The preprocedural administration of Cinryze before dental,
`surgical, or interventional diagnostic procedures was found
`to prevent edematous episodes; in a retrospective analysis
`of data from two acute treatment trials, 89 of 91 procedures
`did not trigger a subsequent HAE attack.46
`The long-term protective efficacy of Cinryze (open label)
`was evaluated in a placebo-controlled crossover study of
`patients with a history of at least two attacks per month.
`These patients were randomly assigned 1,000 units of
`open-label nanofiltered C1-INH concentrate for the preven-
`tion of acute HAE attacks or a placebo, administered twice
`weekly.45 Cinryze had a significant benefit over placebo
`treatment, as evidenced by a reduction in the number of
`attacks per 12-week period (6.26 with C1-INH concentrate
`vs 12.73 with placebo; P,0.001). The severity and duration
`of attacks, the need for open-label rescue therapy, and the
`
`Real-world and home use
`Administration of plasma-derived C1-INH in a health care
`facility may be hindered by accessibility and convenience
`factors, and this is particularly challenging for those who
`require treatment twice per week. This may affect the
`patient’s time needed to receive treatment and patients’
`adherence to the regimen. Home infusion provides an easy
`and convenient modality of C1-INH delivery and use, and
`a significant proportion of patients prefer self-administered
`plasma-derived C1-INH at home (Table 2).
`Home administration with plasma-derived C1-INH con-
`centrates results in reduced frequency of attacks compared
`with previous treatment such as danazol or tranexamic acid,
`fewer days spent in a hospital, and fewer days missed from
`school or work.51,54,55 Overall, self-administration of intrave-
`nous C1-INH concentrate is associated with enhancing the
`quality of life of patients with HAE.51,56
`
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`Utility of C1 esterase inhibitor concentrates for HAe
`
`Levi et al54
`
`Bygum et al56
`
`Kreuz et al55
`
`Kreuz et al51
`
`References
`
`in prophylaxis group, attack rate decreased from 4 to 0.3 per month
`Significantly shorter TOSR (2.2 hours)
`Technical failure rate ,2%
`All patients capable of intravenous self-administration
`No serious complications at 27–72 months, follow-up
`improved SF-36 scores
`After 3–48 months, improved quality of life, DLQi score reduced from 12.6 to 2.7 (P,0.001),
`TOSR reduced from 60 to 40 minutes
`Median time between attack onset and administration reduced from 67.5 to 15 minutes
`No side effects or injection site reactions
`Mean days hospitalized reduced from 3.8 to 0.11/year
`All attacks including laryngeal edema treated
`Significant increase in dosing frequency
`No viral transmission
`24 laryngeal episodes/year ceased
`Median number of attacks/year decreased (P,0.001)
`
`C1-iNH)
`prophylaxis (ten with HAe, two with AAe-
`HAe, three with AAe-C1-iNH) and 12
`31 on-demand treatment (28 with
`
`Seven with severe or frequent symptoms
`
`pediatric (prophylaxis)
`15 pediatric (on-demand treatment) and five
`danazol
`incompatibility or lack of response to
`22 with severe symptoms and
`
`Observational study findings of home therapy
`
`Number of patients in study
`
`Safety and tolerability
`Long-term prophylaxis with Cinryze was well tolerated
`in a placebo-controlled crossover study and its open-label
`extension phase.45,48 The most common AEs observed were
`headache, nausea, rash, and vomiting. A recent systematic
`review of the literature concluded that Berinert also has a
`comparable side effect profile.44
`Hypersensitivity reactions and serious arterial and venous
`thromboembolic events have been reported at the recommended
`dose of Berinert32 and the prescribed dose of Cinryze.38
`The transmission of blood-borne diseases (viruses or pri-
`ons) is an inherent risk for all human plasma-derived products,
`including Cinryze and Berinert (Table 3). In a report of ~260
`patients who received Cinryze in clinical studies, a total of
`~14,000 doses were administered; none of these patients
`became positive for parvovirus B19, hepatitis B, hepatitis C, or
`HIV.38 A review of the literature for Berinert also ascertained
`that it was not associated with transmission of viruses.44
`Overall, numerous studies have demonstrated that home
`administration of HAE medications is safe, with a low occur-
`rence rate of AEs.51,54,56–59
`
`The role of home self-infusion in
`HAE management
`Current clinical guidelines recommend home-based treatment
`where feasible and that all patients have access to medica-
`tion supply at all times.30,60–63 Therefore, a large proportion
`of patients on long-term prophylaxis using Cinryze choose
`the home therapy option. The result is significantly reduced
`HAE-related hospitalizations, androgen-derivative usage,
`and greater patient satisfaction.57,64
`Cinryze, initially approved by the FDA in 2008, was
`approved for self-administration (in patients who receive suf-
`ficient training) by the FDA in June 200965,66 and by the EMA
`in June 2011.67 In June 2010, in a study performed in the US,
`243 of 516 patients (47%, 5–84 years of age) administered
`Cinryze at home, with the remainder of patients receiving
`treatment in the physician’s office or at an infusion center.
`The proportion of patients receiving treatment in a home set-
`ting (ie, 20% of the total study population) who self-adminis-
`tered the drug was 42%, and 16% and 23% of patients were
`administered the drug by a family member or a home health
`care worker, respectively.68 In 2012, following the implemen-
`tation of an infusion training program in December 2010, the
`proportion of patients receiving Cinryze at home (rather than
`at a physician’s office or infusion center) increased to 76%
`and the percentage who self-administered increased from
`20% to 44%.69 In 2010, 30- to 64-year-olds were the largest
`
`TOSR, time to onset of symptom relief.
`Abbreviations: AAE-C1-INH, acquired angioedema due to C1 esterase inhibitor deficiency; C1-INH, C1 esterase inhibitor; DLQI, Dermatology Life Quality Index; HAE, hereditary angioedema; SF-36, 36-Item Short-Form Health Survey;
`
`Berinert®
`name
`Drug
`Table 2 Summary of real-world observational data for home-based HAe therapy with human plasma-derived C1-iNH
`
`tranexamic acid
`Danazol and/or
`
`tranexamic acid
`Danazol and/or
`
`Cetor®
`
`Berinert
`
`Berinert
`administered
`Physician-
`
`Berinert
`
`Danazol
`medicine
`Prior preventative
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`Cetor package leaflet73
`Cetor summary of product characteristics72
`Safety and efficacy not established in children (0–11 years of age)
`administration
`No studies on the ability to drive or operate machines post
`Has not been evaluated in pregnant women or nursing mothers
`
`All considered mild and rare
`Reaction at injection site, rise in temperature (classified as rare)
`product is administered frequently
`Physician may recommend hepatitis A or B vaccination if this
`removal step in purification process)
`theoretically, the Creutzfeldt–Jakob disease agent (only one viral
`Risk of transmission of infectious agents, including viruses and,
`
`Hypersensitivity or anaphylactic shock
`
`headache, dizziness, nausea, anaphylaxis
`Tachycardia, hyper- or hypotension, flushing, hives, dyspnea,
`Cetor®
`
`reactions
`hypersensitivity
`Allergic or
`AEs
`Table 3 Treatment-related Aes associated with commercially available human plasma-derived C1-iNH concentrates for HAe treatment
`
`anaphylaxis
`tightness, wheezing, hypotension, and
`includes hives, generalized urticaria, chest
`Berinert®
`
`Abbreviations: Ae, adverse event; Ci-iNH, C1 esterase inhibitor; HAe, hereditary angioedema.
`
`Cinryze prescribing information38
`Cinryze safety information71
`
`Safety and efficacy not established in children (0–11 years of age)
`Risk associated if taking contraceptive pills or androgens
`Has not been evaluated in pregnant women or nursing mothers
`
`Headache, nausea, rash, and vomiting
`
`Berinert safety information70
`or in the geriatric population
`been established in children (0–12 years of age)
`nursing mothers, and safety and efficacy have not
`Has not been evaluated in pregnant women or
`frequently than in the placebo group)
`Dysgeusia (.4% of patients and more
`increase in the severity of HAe-associated pain
`
`References
`
`Additional risks
`
`Most common
`Most serious
`
`Creutzfeldt–Jakob disease agent
`including viruses and, theoretically, the
`Risk of transmission of infectious agents,
`
`risks
`Plasma-derived
`
`Arterial and venous thromboembolic events
`
`Serious events
`
`theoretically, the Creutzfeldt–Jakob disease agent
`Risk of transmission of infectious agents, including viruses and,
`accidents
`Arterial and venous thromboembolic events, cerebrovascular
`hypersensitivity reaction to the product, including anaphylaxis)
`if the patient has experienced a life-threatening immediate
`facial swelling, faintness, rash, hives (use is not recommended
`breathing, chest tightness, cyanosis (lips and gums), tachycardia,
`Allergic reactions that may occur include wheezing, difficulty
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`Utility of C1 esterase inhibitor concentrates for HAe
`
`age group in which 50% self-administered, but the patient
`group who were reported to be self-administering Cinryze
`excluded children (0–12 years of age) or patients .65 years
`of age.68,69 In 2012, only one child and ten older patients
`were found to be self-administering.69 The percentage of
`patients who received C1-INH at home in 2012 was found
`to be similar across all age groups (#12 to $65 years of
`age). A total of 57.9% of patients receiving home infusions
`of Cinryze did so by self-administration.69
`A European multicenter study of patients with HAE using
`Cinryze showed that the majority of doses (87%) used for
`routine or preprocedural prophylaxis were given at home and
`67% were self-administered.74
`For Berinert, as of May 2013, a multicenter registry across
`the US and the EU found that .90% of intravenous infusions
`for prophylaxis were given by the patient or a caregiver at
`home,75 compared with the 49% uptake rate reported by a
`German center 3 years earlier.57
`Relatively fewer pediatric patients with HAE are given
`long-term C1-INH prophylactic treatment.76 In a UK survey
`of 111 children with HAE, one-third were receiving routine
`preventative medications, of whom only four were receiving
`C1-INH concentrate. Ten of 16 centers were able to offer train-
`ing to administer C1-INH concentrate to children at home, but
`only two patients were participating in this process.76
`
`The model for delivering plasma-derived C1-INH con-
`centrates in a home setting is based on other successful home
`therapy programs, such as those for managing immunodefi-
`ciency, hemophilia, and other chronic conditions.57,77–79 The
`most notable benefit of C1-INH concentrate self-administration
`is flexibility and convenience, thus avoiding regular time-
`consuming visits to the clinic. The process empowers patients
`to take control of their disease to the extent that they can resume
`a normal, less restricted life, without the need to visit a doctor’s
`office for treatment. Although the concept of self-administration
`can be intimidating for both the patient and the physician, the
`provision of appropriate education and training, possibly with
`a few hours of counseling by their health care provider, enables
`most patients to feel comfortable with home therapy.80,81
`However, it should be noted that, despite the fact that all
`patients with HAE requiring long-term prophylaxis using
`C1-INH concentrate are recommended to be considered for
`home therapy,61,62,68 the eligibility of patients for this treat-
`ment is determined by several factors (Table 4). Patients
`may experience several challenges, such as acquiring the
`skill of infusion administration, and other potential barriers
`include managing nursing resources for patient training and
`the patient’s mental capacity.83
`For self-administration with C1-INH concentrate,
`venipuncture using a small (eg, 28G) butterfly needle infusion
`
`expectations
`Mental or physical capacity
`Compliance or reliability
`Maintaining infusion skill set
`Consent
`Awareness of risk
`
`Partner or caregiver
`
`Local family practice support
`
`Communication access
`venous access
`
`Table 4 Patient eligibility criteria for home-based HAe treatment
`References
`Factor
`Patient criteria for home therapy
`Gompels et al16
`Nature of HAe
`CI-INH deficiency
`Kreuz et al;51 Bygum et al56
`Severity and frequency of attacks
`Severe or frequent symptoms
`Efficacy or tolerability of current prophylactic therapies incompatibility or lack of response to danazol or tranexamic acid Kreuz et al;51 Levi et al54
`Current effect of HAe on quality of life
`Serious and affected by delay in visiting emergency departments
`Bygum et al56
`in the event of an attack
`Managed via education, training, and support
`essential for self-administration
`Should be optimal
`infusion required at least once every 3 months
`Should be obtained in written format
`informed of risk of transmissible infection from a plasma-derived
`product
`Available at the time of treatment (particularly important if age
`or disability is a factor)
`Written confirmation of support from general practitioner,
`including preplanned emergency care if required
`Close proximity of a telephone when administering treatment
`Good venous access (current approved treatments are
`intravenous)
`Agreement by patient to call the emergency service if self-
`cannulation is unsuccessful at the time of the HAe attack
`Do the benefits of home therapy outweigh the risks and possible
`side effects for the patient?
`Note: Copyright © 2005. British Society for Immunology. John Wiley and Sons. Adapted from Gompels MM, Lock RJ, Abinun M, et al. C1 inhibitor deficiency: consensus
`document. Clin Exp Immunol. 2005; 139(3):379–394.16
`Abbreviations: Ci-iNH, C1 esterase inhibitor; HAe, hereditary angioedema.
`
`Longhurst et al58
`
`Gompels et al16
`Gompels et al16
`Gompels et al16
`Gompels et al16
`
`Gompels et al16
`Gower et al84
`Gompels et al16
`
`Gompels et al16
`Gompels et al16
`
`Gompels et al16
`
`Cicardi et al61
`
`Plan of action if administration is difficult
`
`Physician’s risk–benefit judgement
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`set is recommended;82 however, safety concerns related to
`this self-administration procedure exist. Findings from an
`observational study of the use of Berinert indicated that all
`AEs (mild cases of redness at the injection site and vertigo)
`occurring after self-administration were due to either intra-
`venous administration that was too rapid or administration
`at a suboptimum temperature (ie, ,25°C).51 Furthermore,
`indwelling venous ports are associated with complications
`such as infection and occlusion that can increase the fre-
`quency of attacks, and hence, they should be avoided when-
`ever possible and only be considered where timely venous
`access is difficult.82 In general, however, cannulation failure
`is uncommon with self-administration after sufficient train-
`ing, and self-administration may support vein preservation
`more than that possible in a hospital setting.54
`
`Summary and future development
`Intravenous administration of C1-INH concentrate is a safe
`and effective strategy for short-term (preprocedural) and
`long-term prophylaxis against HAE attacks. The majority of
`patients who receive Cinryze as a long-term prophylaxis mea-
`sure can safely administer this product at home. Most notably,
`50% of 30- to 64-year-old patients can perform self-infusion.
`The positive outcomes associated with Cinryze in the home
`setting may be even better with subcutaneous formulations
`of plasma-derived C1-INH concentrate, which are currently
`under clinical evaluation. Clinical trials are underway to
`establish whether subcutaneous delivery of plasma-derived
`C1-INH will provide a comparable efficacy benefit. A Phas