Infusion-related Hypersensitivity Research Articles

P013 Resolution of Infliximab Associated Infusion Hypersensitivity After Switching to Biosimilar Infliximab-dyyb.

Background: Administration of infliximab for the treatment of inflammatory bowel disease has a well-recognized risk of infusion-related (IR) adverse events. The recent introduction of the biosimilar infliximab-dyyb (Inflectra®) has been shown to have similar efficacy with comparable safety profile when compared to infliximab; however, although the active ingredients are similar, the inactive ingredients are different. We present a case of a 26-year-old female with ulcerative colitis who had resolution of her IR hypersensitivity when switched from infliximab to infliximab-dyyb. A 26-year-old female with a past medical history of ulcerative pancolitis presented to our clinic with the chief complaint of rash associated with her infliximab infusions. She described pruritic raised lesions which would occur on her upper and lower extremities during her infusions. She denied any shortness of breath or wheezing, and her symptoms were well controlled with methylprednisolone 40mg IV prior to her infusions. Previously, she had been treated for her UC with oral mesalamine, azathioprine and intermittent prednisone and did not have any adverse reactions to these medications. She has no known allergies to other medications and her peripheral eosinophil count was 1.6%. She was initially started on infliximab 5mg/kg every 8 weeks since 2013 and had achieved clinical as well as endoscopic remission with her most recent colonoscopy graded as Mayo 0. On account of her infusion reaction, drug antibodies were checked but were not detected. Infliximab level was 8.8 μg/ml. Due to insurance she was required to switch to infliximab-dyyb. After switching to the biosimilar, she has not had any infusion related reactions and no longer requires premedication with methylprednisolone with her infusions. Immediate IR reactions have been reported in 5-23% of IBD patients receiving infliximab and those who develop antibodies towards infliximab have a 2-fold risk of acute IR events. Side effects have been reported to be the primary reason for discontinuation of infliximab, and studies have shown that discontinuation can lead to an increased risk of relapse of inflammatory bowel disease. Although infliximab and infliximab-dyyb have analogous active ingredients, the inactive ingredients differ. Specifically, infliximab-dyyb lacks monobasic sodium phosphate and dibasic sodium phosphate, which acts as an emulsifier which we believe contributed to her IR with originator biologic infliximab. It is important to recognize these differences as IR hypersensitivities may be attributed to inactive ingredients; especially when antibodies are negative. Our case report suggests that a switch to biosimilar infliximab in patients may provide added benefit especially in those that have reactions occurring from inactive ingredients in the originator biologic.

Long-term safety and tolerability of eptinezumab in patients with chronic migraine: a 2-year, open-label, phase 3 trial

BackgroundEptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody recently approved in the United States for preventive treatment of migraine in adults, was found to be well tolerated in double-blind, placebo-controlled studies in patients with episodic and chronic migraine. The objective of the PREVAIL study was to evaluate the long-term safety, immunogenicity, and impact on patient-reported outcomes of repeat doses of eptinezumab in patients with chronic migraine.MethodsPREVAIL was an open-label, phase 3 trial comprising a 48-week treatment phase followed by a second 48-week treatment phase. Adults with chronic migraine received eptinezumab 300 mg by 30-min intravenous administration every 12 weeks for up to 8 doses. Patients were followed for 20 weeks after the final infusion (end-of-study visit at week 104).ResultsOverall, 128 adults (mean age, 41.5 years) with chronic migraine were included. During the 2 years, the most frequently reported treatment-emergent adverse events were nasopharyngitis (14.1%), upper respiratory tract infection (7.8%), sinusitis (7.8%), influenza (6.3%), bronchitis (5.5%), and migraine (5.5%). The rate of study-drug discontinuation due to adverse events was 6.3%, which included 3 patients with infusion-related hypersensitivity. The incidence of anti-eptinezumab antibodies peaked at week 24 and declined despite continued dosing, to nondetectable levels at week 104. Improvements in patient-reported outcomes were observed at first assessment (week 4) and generally sustained through week 104.ConclusionIn adults with chronic migraine, eptinezumab 300 mg demonstrated a favorable safety profile, limited long-term immunogenicity, early and sustained reductions in migraine-related burden, and improvements in health-related quality of life over 2 years.Trial registrationClinicalTrials.gov (Identifier: NCT02985398).

Infusion related hypersensitivity reaction to enzyme replacement therapy for lysosomal diseases

Infusion related hypersensitivity reaction to enzyme replacement therapy for lysosomal diseases

Simplification of bevacizumab (bev) administration: Do we need 90, 60, or even 30 minute infusion times?

3542 Background: Bev is a humanized monoclonal antibody that targets VEGF. Due to concerns of infusion related hypersensitivity reactions, phase I trials of bev used an initial 90 minute infusion of bev, a 60 minutes for on the next dose, and 30 minutes for all doses thereafter. This has remained the administration schedule throughout development and registration. No significant infusion-related toxicities were reported in the pivotal phase III registration trial. We postulated therefore that bev could be safely given without initially prolonged infusion times. Methods: We obtained an IRB waiver of authorization to review the records of patients at Memorial Sloan Kettering Cancer Center (MSKCC) who were treated with bev in the first 3 months of commercial availability (cut-off date 5/15/05). Our institutional adverse drug reaction reporting program was utilized to identify any infusion reactions related to bev. Additionally, patient medical records were reviewed for further confirmation. Results: Following initial commercial availability of bev in February 2004, 202 consecutive colorectal cancer (CRC) patients were treated with bev (5 mg/kg) at MSKCC starting as a 90 minute, then 60 minute, then 30 minute infusion. No hypersensitivity reactions were seen. A decision was then made to establish an institutional practice of using 30 minute infusion times for all doses, including initial doses, of bev. Subsequently, 212 consecutive CRC patients were treated with bev 5 mg/kg, initially as a 30 minute infusion. No infusion reactions were observed. Conclusions: Administration of the initial dose of bev over 30 minutes appears to be safe and well-tolerated. This has been the standard initial infusion time at MSKCC for 5 mg/kg, 10 mg/kg and 15 mg/kg doses of bev. Based on our favorable experience with 30 minute infusions of 15 mg/kg (0.5 mg/kg/minute), as of Nov ’05 we have changed our institutional guidelines such that all non-protocol patients receiving bev are initiated at the infusion rate of 0.5 mg/kg/minute. Thus, our standard 5 mg/kg doses of bev are given over 10 minutes, 10 mg/kg doses are given over 20 minutes, and 15 mg/kg doses are given over 30 minutes. Active quality assurance and safety monitoring are maintained throughout. Data will be updated for the meeting. [Table: see text]

Phase I dose-escalation trial investigating the safety and tolerability of EPO906 plus gemcitabine in patients with advanced cancer

3100 Background: EPO906, a novel epothilone, is a microtubule stabilizer that has demonstrated clinical cytotoxic activity in taxane-sensitive, -resistant, and -refractory tumors and, unlike taxanes, is not associated with myelosuppression, alopecia, or infusion-related hypersensitivity. EPO906 and gemcitabine, an inhibitor of DNA synthesis, have different mechanisms of action and non-overlapping toxicity profiles and may have synergistic antitumor activity. In a phase I, multicenter trial, we evaluated the safety and tolerability of EPO906 in combination with gemcitabine for the treatment of advanced cancers. Methods: Eligible patients (pts) had stage IV disease with ≥ 1 measurable lesion and performance status grade ≤ 2. Pts received weekly EPO906 via 5-min IV infusion starting at 0.5 mg/m2, immediately followed by gemcitabine 800 mg/m2 via 30-min IV infusion, for 3 wks followed by 1 wk rest. EPO906 was escalated in subsequent cohorts by 0.5-mg/m2 increments to 2.5 mg/m2 (the probable MTD of EPO906 alone for the 3 wk on/1 wk off schedule). Results: In total, 24 pts were enrolled in 5 cohorts treated with 0.5 mg/m2 (n = 4), 1.0 mg/m2 (n = 4), 1.5 mg/m2 (n = 4), 2.0 mg/m2 (n = 6) and 2.5 mg/m2 (n = 6). Median age was 54 yrs (range, 27–75 yrs). No DLTs were reported in pts treated with EPO906 at doses up to 2.0 mg/m2. In the 2.5-mg/m2 cohort, 4 of 6 pts experienced DLTs, including grade (gr) 3 diarrhea (n = 3), nausea (n = 1), and dizziness (n = 1). Thus, the MTD of EPO906 in combination with gemcitabine is 2.0 mg/m2. Most common nonhematologic toxicities (any gr) included diarrhea (n = 15), nausea (n = 15), and fatigue (n = 12). Hematologic toxicities included gr 4 neutropenia (n = 1) and gr 3 anemia (n = 4), neutropenia (n = 3), leukopenia (n = 2), and thrombocytopenia (n = 1). After 2 cycles of therapy, RECIST tumor assessment in 16 evaluable pts showed 1 pt with a partial response and 7 with stable disease. Conclusion: These preliminary data indicate that the combination of EPO906 and gemcitabine is generally safe and well tolerated. Future studies will fully characterize the role of EPO906 in combination with gemcitabine in the treatment of advanced cancers. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. Berlex; Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp. August A. Fink Memorial Foundation Novartis