Stephanie Santucci

Anaphylaxis and serum sickness in patients receiving omalizumab: reviewing the data in light of clinical experience.

Clinical Trial Experience Post-Marketing Data Omalizumab Joint Task Force Yang Medicine of IgE to the high-affinity IgE receptors on the surface of mast cells and basophils, causing a decrease in surface-bound IgE. This results in a decreased level of released mediators that cause the allergic response.1 Omalizumab was approved for use in the United States and Canada in 2003 for patients older than 12 years who are diagnosed with severe allergic asthma. The premarketing clinical trial data showed an incidence of anaphylaxis of less than 0.1% after 3,854 subjects received omalizumab.2 In addition, there were 4 incidents of serum sickness (3 omalizumab-treated subjects and 1 control subject), but in all cases the symptoms resolved despite continuation of treatment.3 After omalizumab’s approval in 2003, data began emerging that the incidence of anaphylaxis could have been higher than reported in the clinical trials. Spontaneous reporting indicated that the frequency of anaphylaxis was at least 0.2% of patients receiving the drug.2 There also were reports of serum sickness in isolated instances.4,5 In 2007, the US Food and Drug Administration (FDA) issued a boxed warning about the risk of anaphylaxis associated with omalizumab.6 After the FDA issued the boxedwarning, the AmericanAcademyof Allergy, Asthma and Immunology formed the Omalizumab Joint Task Force (OJTF).7 The OJTF had the purpose of reviewing omalizumab clinical trial data and postmarketing surveillance data related to anaphylaxis.7 The OJTF’s first report in late 2007 focused on postmarketing data from June 2003 to December 2006. After careful review, the task force concluded that anaphylaxis likely occurred only in approximately 0.09% of patients receiving omalizumab injections, less than half the rate reported (0.2%) by the FDA for that period.7 A second review focused on cases from January 1, 2006 to December 31, 2008. The OJTF reviewed 127 postmarketing cases of possible omalizumab-associated anaphylaxis filed with the FDA and concluded that only 77 of the 127 cases could be probable omalizumab-associated anaphylaxis. The OJTF described the many difficulties in being certain that an adverse event was truly anaphylaxis, although awidely accepted consensus definition for anaphylaxis was used to interpret the adverse event reports. The OJTF noted a wide variation in interpretation of some events with a trend toward being conservative. Some of these events might have been caused by other factors, such as the patients’ underlying poorly controlled asthma. The OJTF reported that it was “highly likely that there was over-reporting of anaphylactic episodes” because they chose to attribute clinical significance to events thatwere not clearly reported.8 We have been administering omalizumab at our site beginning in 1998, during premarketing research phases, to the present day. We have administered more than 22,000 injections of omalizumab

Self-administration of intravenous C1 esterase inhibitor in hereditary angioedema

Hereditary angioedema is a rare autosomal dominant disorder that results in episodes of acute edema in various organs, including the gastrointestinal tract, skin and larynx. It is estimated to affect about 1 in 50 000–100 000 people.[1][1] The symptoms, including abdominal pain, laryngeal edema

Successful use of daily intravenous infusion of C1 esterase inhibitor concentrate in the treatment of a hereditary angioedema patient with ascites, hypovolemic shock, sepsis, renal and respiratory failure

Hereditary angioedema (HAE) is a rare autosomal dominant disease most commonly associated with defects in C1 esterase inhibitor (C1-INH). HAE manifests as recurrent episodes of edema in various body locations. Atypical symptoms, such as ascites, acute respiratory distress syndrome, and hypovolemic shock, have also been reported. Management of HAE conventionally involves the treatment of acute attacks, as well as short- and long-term prophylaxis. Since attacks can be triggered by several factors, including stress and physical trauma, prophylactic therapy is recommended for patients undergoing surgery. Human plasma-derived C1-INH (pdC1-INH) concentrate is indicated for the treatment of both acute HAE attacks and pre-procedure prevention of HAE episodes in patients undergoing medical, dental, or surgical procedures. We report the first case of a patient with HAE who experienced an abdominal attack precipitated by a retroperitoneal bleed while being converted from warfarin to heparin in preparation for surgery. Subsequently, the patient had a protracted course in hospital with other complications, which included hypovolemic shock, ascites, severe sepsis from nosocomial pneumonia, renal and respiratory failure. Despite intensive interventions, the patient remained in a critical state for months; however, after a trial of daily intravenous infusion of pdC1-INH concentrate (Berinert®, CSL Behring GmbH, Marburg, Germany), clinical status improved, particularly renal function. Therefore, pdC1-INH concentrate may be an effective treatment option to consider for critically-ill patients with HAE.

The prophylactic use of C1 inhibitor in hereditary angioedema patients undergoing invasive surgical procedures: a retrospective study

BackgroundHereditary Angioedema (HAE) is a rare autosomal dominant condition characterized by episodic angioedema, which may be triggered by invasive procedures and surgery. C1 inhibitor (C1 INH) was approved in the United States and Canada in 2009 and 2010, respectively, for the treatment of acute attacks. Most recently in April 2013, it was approved in Europe for short-term prophylaxis (STP), prior to medical, dental, or surgical procedures, to prevent HAE attacks in both children and adults. Currently, C1 INH is not approved in Canada or the United States for STP of HAE attacks. Our objective was to demonstrate the effectiveness of C1 INH as a short-term prophylactic treatment for patients with Type I HAE undergoing invasive surgical procedures.MethodsA retrospective chart review between 1997-2013 was performed at one Canadian Tertiary Care Allergy and Asthma Clinic affiliated with The Ottawa Hospital, in Ottawa, Canada. The standard dose of C1 INH for STP was 10 or 20 U/kg.ResultsIn all 24 procedures, there were no post-procedure HAE attacks after short-term prophylactic administration of C1 INH.ConclusionsIn this retrospective chart review at one tertiary care Allergy and Clinical Immunology Clinic, short-term prophylactic use of C1 INH was found to be effective at preventing post-procedure HAE attacks, in patients diagnosed with Type I HAE.

Use of Omalizumab to treat a nine-year old, with steroid-dependent, allergic asthma, adrenal insufficiency and vertebral compression fractures due to steroid induced severe osteoporosis

Background In Canada, Omalizumab is indicated for adults and adolescents with moderate to severe persistent allergic asthma, but not for pediatric use (<12 years of age). A 9 year-old boy with steroid dependent, allergic asthma, multiple ICU admissions and severe back pain from compression fractures was referred to our centre. IgE was 1337 IU/ml. Skin prick testing showed multiple positive reactions. Asthma treatment included inhaled corticosteroids and frequent courses of oral prednisone.

The observed incidence of anaphylaxis and serum sickness in patients receiving omalizumab in a tertiary allergy and asthma clinic in Canada

Conclusion Meticulous care was taken by our omalizumab administration clinic to ensure optimal safety based on the emphasized warnings of anaphylaxis, as well as, the indicated warnings and precautions for serum sickness. Data collected in this analysis observed no cases of anaphylaxis or serum sickness like symptoms in the treatment of over 250 patients, during a period of 15.5 years, who combined received 21,000 injections of omalizumab thus confirming the low incidence of both anaphylaxis and serum sickness. Authors’ details Allergy and Asthma Research Centre, Ottawa, ON, Canada. University of Ottawa Medical School, Ottawa, ON, Canada.

Xolair® (omalizumab) enrollment in a tertiary care allergy and asthma clinic in Canada

Background Xolair ® (omalizumab) has been approved in Canada since 2004 for the treatment of moderate to severe persistent allergic asthma in patients 12 years of age. The use of omalizumab in severe persistent allergic asthma may lead to decrease health care utilization through emergency room (ER) visits, hospitalizations, visits to health care providers, as well as, decrease the use of corticosteroids and improve the overall quality of life (QoL).

Anti-Ige monoclonal antibody therapy for the treatment of patients with chronic rhinosinusitis: a multi-disciplinary practice review

Background Several treatment options have been described for chronic rhinosinusitis (CRS), yet many patients remain poorly responsive to medical and surgical therapy. Recently, antiIgE monoclonal antibody has emerged as a potential therapy for CRS. However, to date evidence for its efficacy in this patient population is sparse. The purpose of this study is to evaluate the clinical effect of anti-IgE monoclonal antibody therapy for patients with recalcitrant CRS and asthma treated in a multi-disciplinary clinic.

Omalizumab treatment of moderate to severe asthma in the adolescent and pediatric population

Background In Canada and the US, omalizumab is indicated for adults and adolescents (>12 years of age) with moderate to severe persistent allergic asthma. In the EU, omalizumab has been approved for children (age 6 – 11 years) since 2009. The pediatric population within Canada and the United States has very few treatment options available for severe asthma. Current treatments options can lead to other health concerns such as adrenal insufficiency and osteoporosis. These cases demonstrate that early treatment of moderate to severe asthma with omalizumab is an effective treatment and can help to prevent or reverse damage done by long-term use of other treatment options.

Self-administration of a novel subcutaneous bradykinin b2 receptor antagonist, icatibant, as an effective treatment option in patients with hereditary angioedema

Background Hereditary Angioedema (HAE) is a rare disease characterized by recurrent angioedema attacks involving larynx, abdomen, extremities and various body parts. The reactions are by and large self-limited, but potentially, could be fatal. Until recently, the only approved treatment in Canada is an intravenous C1-esterase inhibitor infusion. However, intravenous therapy can be challenging for those who have co-morbid disorders. Icatibant (Firazyr) —which received approval in Canada in June 2014 — offers administration through subcutaneous delivery. Through a special access program, here we present self-administered icatibant treatment on a female subject with Charcot-Marie-Tooth disease, a rare genetic, neuromuscular disorder, which limits her ability to self-administer intravenous therapy.