Rapid Drug Desensitization Protocol Research Articles

Rapid drug desensitization protocol in delayed hypersensitivity reactions to CFTR modulator drugs: When everyday counts.

Rapid drug desensitization protocol in delayed hypersensitivity reactions to CFTR modulator drugs: When everyday counts.

Rapid drug desensitization to taxanes: a descriptive study from Turkey.

To present the characteristics of drug hypersensitivity reactions (DHRs) among taxane recipients with non-small cell lung carcinoma (NSCLC), and to describe the results of rapid drug desensitization (RDD). A retrospective cross-sectional study included 45 patients who were treated with taxane for NSCLC and were found to be hypersensitive to taxane. All patients were administered the standard 3-bag, 12-step RDD protocol following the development of DHR. RDD success was evaluated separately for each cycle, and successful RDD was defined as the completion of the cycle with application of 12 steps of the desensitization protocol and the absence of early and/or late reactions afterwards. Among 45 patients hypersensitive to taxane 43 (95.6%) successfully received taxane cycles with desensitization. Failed RDD occurred in only 2 (4.4%) patients. The total number of desensitization cycles was 183, of which 181 (98.9%) were successful. The mean age of patients with successful desensitization was 59.42 ± 10.48 years and 37 (86.0%) of them were male. RDD is a reliable procedure that enables effective administration and completion of first-line taxane treatments in taxane-sensitive patients.

Use of Rapid Drug Desensitization in Delayed Hypersensitivity Reactions to Chemotherapy and Monoclonal Antibodies.

Background:Rapid drug desensitization (RDD) allows first-line therapies in patients with immediate drug hypersensitivity reactions (DHR) to chemotherapeutic drugs (ChD) and monoclonal antibodies (mAb). Desensitization in delayed drug reactions has traditionally used slow protocols extending up to several weeks; RDD protocols have been scarcely reported.Patients and Method:We retrospectively analyzed the patients referred to the Allergy Department, who had experienced a delayed DHR (> 6 h) related to a ChD or mAb and underwent an RDD protocol. The rate of successful administration of the offending drug and the presence of adverse reactions were evaluated.Results:A total of 93 RDDs were performed in 11 patients (including 6 men and 5 women, with a median age of 61 years). The primary DHR were maculopapular exanthema (MPE) (8), generalized delayed urticaria (1), MPE with pustulosis and facial edema (1), and facial edema with desquamative eczema (1). The meantime for the onset of symptoms was 3 days (range 1–16 days). RDD was performed using a protocol involving 8–13 steps, with temozolomide (25), bendamustine (4), rituximab (9), infliximab (24), gemcitabine (23), and docetaxel (8), within 4.6–6.5 h. Sixteen breakthrough reactions were reported during the RDD (17.2 %) in 5 patients; all were mild reactions including 11 delayed and 5 immediate reactions. All patients completed their treatment.Conclusions:RDD is a potentially safe and effective procedure in patients suffering from delayed reactions to ChD and mAb. It allows them to receive full treatment in a short period, thereby reducing time and hospital visits.

Rapid drug desensitization with platin-based chemotherapy: Analysis of risk factors for breakthrough reactions

BackgroundAll platin-based chemotherapeutics can cause hypersensitivity reactions (HSRs). With rapid drug desensitization (RDD), few patients experience breakthrough reactions (BTR) during desensitization. However, data about risk factors for BTRs during RDD in patients with HSRs to platins are limited. We first aimed to describe characteristics of our platin-reactive population and to validate the Brigham and Women's Hospital's (BWH's) RDD protocol in our population along with their outcomes with RDD. Our second aim was to identify the risk factors for BTRs. MethodThis was a retrospective chart review (2013–2020) of patients with symptoms of immediate HSRs to platins. Initial HSRs were classified as grade 1, 2, or 3 based on their severity. Skin prick tests (SPT)/intradermal tests (IDT) were performed with implicated platins. A 12-step protocol was used during RDD. ResultsThe study comprised 65 women and seven men (mean age 57.78 ± 8.73 years). Initial HSRs to carboplatin, cisplatin, and oxaliplatin occurred in 38, 13, and 21 patients, respectively. All patients reacted at the fifth (median) recurrent infusions (min:1, max:20). The median values for carboplatin, cisplatin, and oxaliplatin were 6 (1–20), 3 (1–15), and 3 (1–11), respectively. Most initial HSRs were grade 2 (n = 40, 55.6%) and 3 (n = 27, 37.5%); only 6.9% (n = 5) were grade 1. Patients with grade 1, 2, and 3 initial HSRs had positive platin skin test results at rates of 80%, 74%, and 88%, respectively.A total of 232 RDDs were performed in 72 patients and 98.7% of these desensitizations were completed. BTRs occurred in 56 (24.1%) (grade 1 n = 14, 25%; grade 2 n = 32, 57%; grade 3 n = 10, 18%) of these desensitizations. Breakthrough reactions were more severe in patients with positive SPTs or 1:100 or 1:10 dilutions of IDT (p = 0.014). BTR was not observed during RDD in any of the patients with positive 1:1 dilutions of IDT. Positivity on prick or 1:100 or 1:10 IDT increased the risk of BTR 5.058 times. There was no significant association between the risk of BTRs and age, drug cycle, sex, comorbidities, or atopy. ConclusionIn our experience, 98.7% of 232 RDDs to platins were completed successfully, showing that RDD was safe and effective. Drug skin test positivity is a potential marker for identifying high-risk patients who will have BTRs during RDDs to platins.

Evaluation of desensitization protocols to betalactam antibiotics.

Betalactam antibiotics are the most frequent cause of hypersensitivity reactions. Rapid drug desensitization (RDD) is a technique that induces temporary tolerance to a drug allowing a patient to receive the optimal agent. The increased use of RDD and the lack of standardization among available protocols in terms of formulation, starting dose, number of steps and dosing frequency make it essential to determine the safety and appropriate management of these protocols, especially regarding reconstitution, diluents, stability and drug administration in order to guarantee reproducibility. We reviewed betalactam desensitization protocols in a tertiary hospital, in accordance with currently published practices and evaluated its use on patients over a period of three years. (a) We performed a literature search in PubMed, MEDLINE and Google Scholar databases for case reports and/or systematic reviews describing desensitization protocols for betalactam antibiotics. Pharmacokinetic parameters and physicochemical stability were checked for each antibiotic. (b) We retrospectively reviewed inpatients undergoing our antibiotic desensitization protocols from February 2018 to January 2021. Data and outcomes of desensitization procedures were analysed. We developed nine RDD protocols: meropenem, ceftriaxone, ceftazidime, ampicillin, ceftolozane/tazobactam, cloxacillin, piperacillin/tazobactam, amoxicillin/clavulanate and penicillin G sodium. Five antibiotics have RDD protocols for two different doses, adjusted to patients with impaired renal function. Detailed data (diluent, total dose, volume, concentrations, duration and stability) of the protocol of each antibiotic used are provided. 28 desensitizations were performed in 17 patients, three of them with confirmed allergies by skin test. 26 out of 28 (92.9%) of them were successfully completed, including those three with positive skin results. The pathogens most frequently involved were E. faecalis and P. aeruginosa; both frequently associated with bacterial resistance. Meropenem, ceftriaxone and ceftazidime were the antibiotics most desensitized. 25 out of 26 (96.1%) procedures were successful in resolving the infection. Detailed information about compounding, dilution and stability is crucial to ensure safe and successful desensitization processes, as well as good coordination between the Allergy and Pharmacy departments. The increase in bacterial resistance to many of the commercially available antibiotics limits the therapeutic options for treating multidrug-resistant infections; in those situations, antibiotic desensitization may be a key therapeutic option. Although there is a broad consensus in limiting the use of RDD to patients with confirmed allergy, in usual clinical practice its application in those strongly suspected of having type I hypersensitivity is still observed. Our betalactam desensitization protocols have shown themselves to be safe and effective, as evidenced by data from the 17 patients on whom they have been tested.

1715P Rapid drug desensitization (RDD) to anticancer drugs: A 4-year monocentric experience

Hypersensitivity reactions (HRSs) to cancer therapies can be unpredictable and lead to treatment discontinuation, with a negative impact on the patient's prognosis and quality of life. RDD has become a groundbreaking approach to the management of immediate HRSs. However, the lack of guidelines makes the use of RDD at the different cancer centers heterogenous. We present a 4-year experience with the use of RDD protocols at our Oncology Unit.

Desensitization to penicillin is safe and effective in allergic pregnant women with syphilis

Penicillin is the only effective treatment of pregnant women with syphilis. The study assessed the safety and efficacy of risk stratification for guiding penicillin re-introduction in pregnant women with syphilis and penicillin-allergy history. Pregnant women with syphilis and history of immediate hypersensitivity reaction (HSR) to penicillin were enrolled. According to the risk stratification, patients were re-exposed to penicillin either through Rapid Drug Desensitization (RDD), Drug Provocation Test (DPT) or regular administration. Patients with clinical history suggestive of penicillin-anaphylaxis, or positive serum specific IgE, or positive immediate skin test were considered at high risk to react during drug administration and were desensitized. We evaluated 63 pregnant women with latent syphilis and history of penicillin allergy. Thirty-nine patients (61.9%) had clinical history suggestive of immediate HSR and were desensitized. All patients presented negative serum specific IgE and prick test. Intradermal tests were positive in 7/63 (11.1%). Three of them were submitted to an oral protocol and reacted during RDD; one desensitization was not completed. Four patients underwent and completed RDD with an intravenous protocol, and only one reacted. There was an association between positive intradermal tests and breakthrough reactions during RDD (p<0.0001). Patients that had negative intradermal test did not react during RDD. The intravenous protocol was safer than the oral protocol (p = 0.047). The other 24/63 (38.1%) patients considered of low risk were challenged with penicillin and only one reacted (1.6%). Risk stratification and RDD were safe and effective. Intradermal skin testing identified patients with increased risk of reaction during RDD. More patients should be included in the study to confirm the superiority of the intravenous RDD protocol.

Rapid desensitization to antineoplastic drugs in an outpatient immunoallergology clinic: Outcomes and risk factors

BackgroundHypersensitivity reactions to antineoplastic agents may lead to discontinuation of first-line treatments. Rapid drug desensitization (RDD) allows for a safe reintroduction in patients who are allergic to them. ObjectiveTo evaluate the safety and efficacy of the Brigham and Women's Hospital’s 12-step RDD in a Portuguese patient population with cancer and to identify markers associated with breakthrough reactions (BTRs) to platins. MethodsWe conducted a retrospective review of desensitizations undertaken at the Immunoallergology Day-Care Unit of the Santa Maria Hospital in Lisbon, Portugal, from July 2008 to July 2019. Adult patients with cancer and with immediate hypersensitivity reactions were included. Skin testing was performed to platins, trastuzumab, and cetuximab. The 12-step protocol was used for most patients, and a shorter protocol was used in 9 patients who were taxane-reactive to resume regular infusions. ResultsA total of 1471 RDDs were performed in 272 patients to 136 platins, 124 taxanes, 13 monoclonal antibodies, and 10 other drugs. Skin test results were positive in 127 of patients who were platin-reactive (95.3%) and negative in patients who were cetuximab- and trastuzumab-reactive. There were 141 BTRs during RDD (9.6% of infusions), 79.4% induced by platins with the majority having mild reactions (68.8%). There were 8 patients who were paclitaxel-reactive, and who completed a shorter protocol and resumed regular infusions successfully. Multiple platin infusions (cutoff: ≥10) and total immunoglobulin E greater than or equal to 100 U/mL were identified as independent risk factors for BTRs in patients who were platin-reactive. ConclusionThis large single-center study confirmed the safety and efficacy of the 12-step RDD protocol in a diverse cancer population, providing evidence of its universal applications. Total immunoglobulin E is a potentially useful biomarker to identify high-risk patients who are platin-reactive.

Update on Desensitization

Rapid drug desensitization (RDD) is a high-risk protocol that allows patients with hypersensitivity reactions to remain on first-line therapy for their underlying conditions through titration of dose increments and infusion rates. The aim of this paper is to review the most recent desensitization protocols available for drugs that are commonly used in clinical practice settings and to provide algorithms for their appropriate usage. RDD protocols involve identification of phenotypes and endotypes during the initial reaction, risk stratification, skin testing, and specific biomarkers. Patients’ protocols are personalized and can increase life expectancy and quality of life. The benefits of RDD largely outweigh the risks. All patients with hypersensitivity reactions should be evaluated for desensitization, to avoid alternatives treatments that may be less effective or intolerant patients presenting with SCARS (DRESS/SJS/TEN) are not candidates for desensitization since the mechanism of the reactions are poorly understood.

Rapid Drug Desensitization with Chemotherapeutics (Platins, Taxanes, and Others): A Single-Center Retrospective Study

Background: Rapid drug desensitization (RDD) induces a temporary tolerance to chemotherapeutics that induce hypersensitivity reactions (HSRs). Purpose: Our objective is to report our experience with RDD to platins, taxanes, etoposide, doxorubicin, and irinotecan. Methods: The study was conducted as a retrospective chart review of patients with symptoms of HSRs to chemotherapeutics. HSRs were classified as grade I, II, or III, based on their severity. Skin prick/intradermal tests were performed with implicated chemotherapeutics. A 12-step RDD protocol was used. Results: The study consisted of 38 women and 3 men (mean age 53.3 ± 11.6 years). Patients had ovarian (n = 13, 31.8%), breast (n = 10, 24.4%), colon (n = 7, 17%), lung (n = 4, 9.8%), and other cancers (n = 7; endometrial sarcoma, testicular cancer, uterine cancer, ampulla of Vater tumor, choledochal tumor, peritonitis carcinomatosa, and Merkel cell carcinoma, n = 1, respectively). Twenty-two patients experienced HSRs to platins, 15 to taxanes, and 4 to other chemotherapeutics (doxorubicin, irinotecan, and etoposide). A total of 122 RDDs (47 to platins, 52 to taxanes, 23 to other chemotherapeutics) were performed. In 25 (61%) patients no reactions occurred during RDD, but breakthrough reactions developed in 16 patients (39%) with platins (n = 11), taxanes (n = 3), doxorubicin (n = 1), and irinotecan (n = 1). RDD procedures could not be completed in only 2 patients with grade II breakthrough reactions to carboplatin and oxaliplatin. Conclusion: In our experience, 98.3% of 122 RDDs were completed. We found that RDD was safe and effective in this the largest series of RDD with chemotherapeutics in our country.

Rapid Drug Desensitization with Biologics: A Single-Center Experience with Four Biologics

Background: Rapid drug desensitization (RDD) induces a temporary tolerance to biologics which induce hypersensitivity reactions (HSRs). Data are limited regarding the use of RDD outside the USA. Our purpose was to report our data on RDD to rituximab, infliximab, cetuximab, and trastuzumab. Methods: The study was conducted as a retrospective chart review of patients with symptoms of HSRs to biologics. HSRs were classified as grades I, II, and III, based on their severity. Skin-prick tests/intradermal tests (IDTs) were performed with the implicated biologics. The 12-step RDD protocol was used. Results: The study group comprised 11 women and 6 men (mean age: 47 ± 11.7 years). Fourteen patients experienced HSRs to rituximab; 3 had HSRs to cetuximab, infliximab, and trastuzumab, respectively. HSRs to cetuximab, infliximab, and trastuzumab occurred during the first infusion and were all grade III. Twelve of the 14 patients with rituximab hypersensitivity had a reaction during the first infusion; 10 patients had grade II reactions and 4 had grade III reactions. Respiratory symptoms were the most frequent presentation of HSR. Skin tests with rituximab were performed on 10 patients; only 3 resulted in positive IDTs (with 1:100 dilutions) and the other tests were negative as were those performed with the other biologics. Of 96 RDDs, 89 desensitizations were performed with rituximab, 5 with cetuximab, 1 with infliximab, and 1 with trastuzumab. There were 12 (13.5%) breakthrough reactions, all of which were associated with rituximab and were less severe than the initial reactions. Conclusion: RDD was found to be safe and effective in the largest case series of RDDs with biologics in our country, Turkey.

Safety, Costs, and Efficacy of Rapid Drug Desensitizations to Chemotherapy and Monoclonal Antibodies

Rapid drug desensitization (RDD) is used to address hypersensitivity reactions to chemotherapeutics and monoclonal antibodies, allowing patients to be treated with optimal pharmacological agents. RDD protocols are tailored to each individual patient's reaction and needs, and protect against anaphylaxis, but overall risks, costs, and benefits have not been determined. We investigated the safety, efficacy, costs, and life expectancy of patients in a large population undergoing RDD. We analyzed 2177 RDD procedures performed in 370 patients with cancer, vasculitis, and hematological and connective tissue diseases who presented 402 reactions. A subgroup of carboplatin allergic patients with ovarian cancer treated with RDD was analyzed for costs and life expectancy and compared with a nonallergic control group. RDD allowed all patients to receive safely the full dose of the medication to which they were reactive. A gradual increase in the fraction of outpatient desensitizations from 81% to 98% was achieved through risk stratification. Of the 2177 desensitizations, 93% had no or mild reactions whereas 7% had moderate to severe reactions, which did not preclude the completion of the treatment, and there were no deaths. Overall health costs in the carboplatin allergic group were not higher than those in the nonallergic group treated with standard of care. Administration of carboplatin through RDD was as effective as standard administration with a nonsignificant increase in life expectancy in desensitized patients as compared with nonallergic, nondesensitized controls. RDD is cost effective and safe for allergic patients with cancer and chronic disease to remain on first line therapy.

Successful rapid desensitization to intravenous etoposide using a 14-step protocol

Chemotherapeutic agents used for treating neoplastic disease have the potential to induce hypersensitivity reactions (HSRs). With an increase in the use of these drugs, the potential for HSRs has also increased and more cases are frequently being reported. According to Cernadas et al, drug hypersensitivity accounts for more than 15% of all adverse drug reactions, affecting more than 7% of the general population and 10% to 20% of all hospitalized patients. Because these reactions often require the discontinuation of first-line therapies to avoid a life-threatening situation, oncologists have been increasingly consulting allergists to assist in the management of these HSRs. Available options to solve the problem in the presence of HSRs include changing drugs, premedicating with antihistamines and corticosteroids, and/or desensitization. Unfortunately, prescribing an alternative medication is not always feasible especially in the case of targeted therapies, which demand the use of a specific drug. Although a premedication treatment can diminish or prevent the risk of HSRs, it is not sufficient by itself because these drugs often only mask early signs of HSRs rather than prevent them. Etoposide, an antimitotic epipodophyllotoxin active against numerous malignant conditions including germ cell neoplasms, lymphomas, and carcinomas is reported to induce HSRs in 6% of the patients. However, its incidence of anaphylaxis is 0.7%. Manifestations of HSRs to etoposide vary but tend to include bronchospasms, dyspnea, and hypotension. Multiple desensitization studies and case reports have suggested that HSRs to chemotherapeutic agents can be avoided with low infusion rates and managed with the use of pretreatments that include antihistamines and corticosteroids. We present a case in which a 79-year-old woman with limitedstage small cell lung carcinoma was admitted to Mercy Hospital andMedical Center in Chicago for oncology treatment. As she was receiving her second cycle of intravenous etoposide, she developed an anaphylactic reaction. Five minutes into the etoposide infusion, the patient immediately became dyspneic, tachypneic, tachycardic, and hypotensive, developed generalized pruritus with dermatographia, and had oxygen desaturation. She described feeling a sensation she would refer as “taking me out of the world,” notified the nurse, and the treatment was stopped. Given the instantaneous onset of HSR manifestations, it was concluded that etoposide was responsible because no other chemotherapeutic was being administered. Six days later, she was admitted to the hospital for desensitization to etoposide by the immunology service because etoposide was the most suitable chemotherapeutic option for her condition given the drug’s unique mechanism of action. Castells et al developed a standard 12-step rapid drug desensitization (RDD) protocol that involves the infusion of the target dose in 12 incremental steps over a multiple-hour time span. Following the 12-step RDD protocol, we decided to implement the procedure with slight variations; given the patient’s poor performance status, 2 additional steps were added to administer the dose over a longer time span, giving a total of 14 steps. A premedication treatment was given before desensitization to diminish the risk of breakthrough reactions. This included the following:

A new humanized in vitro model of IgE‐mediated rapid desensitization

Background Rapid drug desensitization (RDD) is widely used to re-introduce medications that have caused an IgEmediated hypersensitivity in allergic patients. However, RDD protocols are largely based on empiric experience and few in vitro models have explored the rationale guiding the rate at which the dose should be increased, what the starting dose should be and how the time elapsed between doses affect the effectiveness of desensitization. This study addresses these issues in a new humanized in vitro model of rapid desensitization.

Drug Desensitization in the Management of Hypersensitivity Reactions to Monoclonal Antibodies and Chemotherapy

Hypersensitivity reactions to monoclonal antibodies and chemotherapy, which may vary in severity from mild to life-threatening, can lead to their discontinuation and replacement by alternative agents that are often less effective, more toxic, and/or more expensive. Drug desensitization has emerged as the best treatment modality capable of allowing re-introduction of the hypersensitivity reaction-inducing medication in highly sensitized patients in need of first line therapies. In recent years, the availability of new anti-neoplastic drugs and therapeutic monoclonal antibodies has increased, as has the potential for hypersensitivity reactions. Development of desensitization protocols for these new medications requires a careful assessment of the potential risks and benefits. The purposes of this review are to provide an overview of the presentation of hypersensitivity reactions amenable to desensitization and to increase awareness of the indications for and outcomes of desensitization protocols. Rapid drug desensitization has proven to be a safe and effective way of administering first line therapy to patients with hypersensitivity reactions, providing an extremely powerful treatment modality for patients for whom alternative drugs are deemed unacceptable. Rapid drug desensitization protocols should be administered only by highly trained allergists and nurses who have experience in determining which reactions are amenable to desensitization, and can identify high risk patients and provide them with appropriate care. Efforts should be made to increase awareness of the remarkable safety and efficacy of rapid drug desensitization among non-allergists, especially in the fields of oncology and rheumatology, so as to favor its universal application. Development of desensitization units to provide state-of-the-art care is possible only through coordinated teamwork.

Successful Implementation of a Standardized Rapid Drug Desensitization Protocol for Chemotherapy and Rituximab in 413 Cases

Successful Implementation of a Standardized Rapid Drug Desensitization Protocol for Chemotherapy and Rituximab in 413 Cases