First 1.5 years of pegvaliase clinic: Experiences and outcomes

Sacharow, Stephanie; Papaleo, Cassandra; Almeida, Kyla; Goodlett, Benjamin D.; Kritzer, Amy; Levy, Harvey L.; Martell, Leslie; Wessel, Ann; Viau, Krista

doi:10.1016/j.ymgmr.2020.100603

Cited by 17 publications

(20 citation statements)

References 8 publications

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“…anaphylaxis) or atypical reactions. Patients with acute systemic hypersensitivity events/anaphylaxis are overrepresented in this case series versus previous reports [ 6 , 12 ] because the guidance shared on these cases is important as they require more specific and tailored care.…”

Section: Discussion: Key Learnings Of the Case Series ( Table 3 )mentioning

confidence: 94%

“…sedation may occur even with nominally non-sedating antihistamines); timing of injections in the evening may therefore be preferred (case 7). If premedication is started days before the first injection, the provider can assess any AEs as related to the premedication, as opposed to those related to pegvaliase, and adjust the specific premedication as necessary [ 12 ].…”

Section: Discussion: Key Learnings Of the Case Series ( Table 3 )mentioning

confidence: 99%

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Use of pegvaliase in the management of phenylketonuria: Case series of early experience in US clinics

Adams

Andersson

Bausell

et al. 2021

Molecular Genetics and Metabolism Reports

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Objective To present a case series that illustrates real-world use of pegvaliase based on the initial experiences of US healthcare providers. Methods Sixteen healthcare providers from 14 centers across the US with substantial clinical experience in treating patients with phenylketonuria (PKU) with pegvaliase in the two-plus years since FDA approval (May 2018) provided cases that exemplified important lessons from their initial experiences treating patients with pegvaliase. Key lessons from each case and takeaway points were discussed in both live and virtual meetings. Results Fifteen cases of adults with PKU (eight males, seven females), representing a spectrum of age (18 to 53 years), previous PKU care, comorbidities, and socioeconomic situations were reviewed and discussed. Full extended case reports are included in the Supplement. The cases showed that treating patients with a daily injectable can be challenging due to a patient's financial problems, treatment challenges, and neuropsychological and psychiatric comorbidities, which can be identified before starting pegvaliase, but do not prohibit successful treatment. The authors agreed that patient education on adverse events (AEs), time to efficacy, dietary changes, and food preparation is an ongoing process that should start prior to initiating pegvaliase treatment. Treatment goals and planned dietary changes once efficacy is reached should be defined prior to treatment initiation and re-evaluated throughout the course of therapy. Each patient's titration schedule and dietary adjustments are unique, depending on occurrence of AEs and individual goals of treatment. Despite the AE profile of pegvaliase, all but two patients remained motivated to continue treatment and achieved efficacy (except one patient in whom titration was still ongoing). AEs occurring early in the treatment pathway may require prolongation of the titration phase and/or concomitant medication use, but do not seem indicative of future tolerability or eventual efficacy. Close follow-up of patients during titration and maintenance to help with dietary changes is important. Conclusion This case series provides real-world experience on the use of pegvaliase. Until data from registries and independent research become available, the data presented herein can support appropriate management of patients receiving pegvaliase in clinical practice.

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Section: Discussion: Key Learnings Of the Case Series ( Table 3 )mentioning

confidence: 94%

Section: Discussion: Key Learnings Of the Case Series ( Table 3 )mentioning

confidence: 99%

Use of pegvaliase in the management of phenylketonuria: Case series of early experience in US clinics

Adams

Andersson

Bausell

et al. 2021

Molecular Genetics and Metabolism Reports

Self Cite

View full text Add to dashboard Cite

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“…Early research shows pegvaliase effectively lowering phenylalanine levels, enabling individuals to increase the natural protein in their diets [46]. However, there are reports of hypersensitivity reactions and side effects related to the medication [47]. The most severe reaction being anaphylaxis.…”

Section: Pegvaliasementioning

confidence: 99%

“…The most severe reaction being anaphylaxis. Other reported adverse events include injection site erythema, arthralgia, and headache among others [47]. Immune system activation can be expected, but lessening of this may occur over time [48,49].…”

Section: Pegvaliasementioning

confidence: 99%

“…Immune system activation can be expected, but lessening of this may occur over time [48,49]. Many clinical trial patients achieved sustained reductions in phenylalanine levels [47] Pegvaliase appears to be effective in lowering phenylalanine levels for people regardless of with PAH deficiency phenotypes [46]. Longo et al developed recommendations for treating adults with pegvaliase, and there is a need for long-term research on the safety, dosing, and management of patients using pegvaliase in this newly approved treatment [50].…”

Section: Pegvaliasementioning

confidence: 99%

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Similarities and differences in key diagnosis, treatment, and management approaches for PAH deficiency in the United States and Europe

Lowe

DeLuca

Arnold

2020

Orphanet J Rare Dis

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Background Individuals with phenylalanine hydroxylase (PAH) deficiency lack an enzyme needed to metabolize the amino acid, phenylalanine. This leads to an increase of phenylalanine in the blood, which is associated with changes in cognitive and psychological functioning. Skilled clinical management is essential for preventing complications and providing comprehensive care to patients. In the last decade, the American College of Genetics and Genomics (ACMG) and a group of European experts developed separate guidelines to provide recommendations for the management and care of persons with PAH deficiency. The purpose of this paper was to compare and contrast these guidelines in order to understand the different approaches to PAH deficiency care. Methods We examined the procedures used to develop both guidelines, then evaluated key areas in PAH deficiency care which included screening, diagnostic approaches, dietary treatment (initiation and duration), ongoing phenylalanine level/ nutritional monitoring, neurocognitive screening, adherence issues in treatment, and special populations (women and maternal PKU, late or untreated PAH deficiency, and transitioning to adult services). We conducted a scoping review of four key topics in PAH deficiency care to explore recent research studies performed since the publication of the guidelines. Results The ACMG and European expert group identified limited numbers of high quality studies to use as evidence for their recommendations. The ACMG and European guidelines had many similarities in their respective approaches PAH deficiency care and recommendations for the diagnosis, treatment, and management for persons with PAH deficiency. There were also a number of differences between the guidelines regarding the upper range for phenylalanine levels in adolescents and adults, the types of instruments used and frequency of neuropsychiatric examinations, and monitoring of bone health. Treatment adherence can be associated with a number of challenges, such as aversions to medical foods and formulas, as well as factors related to educational, social, and psychosocial issues. From the scoping review, there were many new studies addressing issues in treatment and management including new research on sapropterin adherence and increased dietary protein tolerance and pegvaliase on the reduction in phenylalanine levels and hypersensitivity reactions. Conclusions In the last decade, ACMG and European experts developed comprehensive guidelines for the clinical management of phenylalanine hydroxylase deficiency. The guidelines offered background and recommendations for clinical care of patients with PAH deficiency throughout the lifespan. New research evidence is available and updates to guidelines can keep pace with new developments. Evidence-based guidelines for diagnosis and treatment are important for providing expert care to patients.

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Milestones in treatments for inborn errors of metabolism: Reflections on Where chemistry and medicine meet

Vernon

Manoli

2021

American J of Med Genetics Pt A

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From Sir Archibald Garrod's initial description of the tetrad of albinism, alkaptonuria, cystinuria, and pentosuria to today, the field of medicine dedicated to inborn errors of metabolism has evolved from disease identification and mechanistic discovery to the development of therapies designed to subvert biochemical defects. In this review, we highlight major milestones in the treatment and diagnosis of inborn errors of metabolism, starting with dietary therapy for phenylketonuria in the 1950s and 1960s, and ending with current approaches in genetic manipulation.

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First 1.5 years of pegvaliase clinic: Experiences and outcomes

Cited by 17 publications

References 8 publications

Use of pegvaliase in the management of phenylketonuria: Case series of early experience in US clinics

Use of pegvaliase in the management of phenylketonuria: Case series of early experience in US clinics

Similarities and differences in key diagnosis, treatment, and management approaches for PAH deficiency in the United States and Europe

Milestones in treatments for inborn errors of metabolism: Reflections on Where chemistry and medicine meet

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