The Impact of COVID-19 on Pediatric Patients with Neurofibromatosis Type 1 PN Clinical Care: A Nurse’s Perspective

By Kasey Rangan, MSN, CPNP, CPHON

Promoted by: AstraZeneca

September 2021

The COVID-19 pandemic has profoundly impacted healthcare. During the initial wave of the US pandemic in March 2020, many states initiated stay-at-home orders and health safety guidelines. These regulations had a dramatic impact on both access to and delivery of healthcare. ¹ As resources were diverted to address the pandemic and care for COVID-19 patients, many people with chronic diseases missed regular screenings and checkups. ¹

But the need for management and prevention of chronic conditions does not disappear during a pandemic. For families of children with the rare genetic disorder, neurofibromatosis type 1 (NF1) with plexiform neurofibroma (PN), a diagnosis begins a patient’s journey of in-person physical examinations, clinical/laboratory assessments, and imaging. ² Partially or severely disrupted routine care services can have a significant impact on patients. ¹

While NF1 PN are benign tumors, pediatric oncology nurses can play a lead role in supporting patients with NF1 PN and their caregivers impacted by COVID-19. Nurses may help families to seek or continue care during the pandemic, as well as educate about ways to safely reengage with the healthcare system. Navigating NF1 PN care delivery during this unprecedented time comes with potential challenges and barriers for both patients and providers.

Barriers to NF1 PN Care

Since there is a variation in the distribution of NF1 treatment centers across the US, pediatric patients with NF1 PN and caregivers may face logistical barriers to receiving care even in “normal” times; these challenges are especially magnified during a pandemic. Parents and caregivers must advocate for their child’s needs at school and overcome the logistical hurdles of working from home while supporting their child’s remote learning.

Compounding these challenges, many NF1 PN treatment centers are operating at limited capacity because of COVID-19. ¹ Not only are caregivers finding it difficult to get or keep appointments at these centers, ¹ but many families are delaying or skipping doctor visits amid the risks that potential exposure to COVID-19 poses. In addition, there is a general feeling among some caregivers and doctors that routine, non-urgent NF1 PN checkups “can wait” until after the pandemic.

To meet the needs of families living with NF1 PN, treatment centers have largely pivoted from face-to-face medical care to telehealth. ¹ A recently published survey of 63 NF clinics (52 clinic directors completed the survey) identified the impact of the pandemic on clinician role, continuity of guideline-driven surveillance, and use of (satisfaction with) telehealth for delivery of care during the month of April 2020. ¹ The survey found that only 1 of the clinics surveyed was using telehealth for follow-up patient visits prior to COVID-19, ¹ that 51 (98%) of the surveyed clinics instituted telehealth during the pandemic, and that 79% conducted urgent visits via telehealth. ¹ Overall, 63% of the clinics reported being satisfied or very satisfied with the use of telehealth services; however, 72% of clinicians indicated they were not satisfied with telehealth as it was suboptimal to perform a physical examination. ¹ All clinics reported that patients were able to have urgent MRIs; however, 43% of clinics reported postponing non-urgent MRIs, and 16% reported that non-urgent testing could not be performed. ¹ In addition, nearly two out of three clinic directors (63%) said they were deferring treatment discussions until the child’s next appointment and 12% said they were waiting to start new patients on treatment until after the pandemic. ¹ Even in the time of a pandemic, it is important to keep up with testing and screenings and to encourage caregivers to make a plan for care.

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Opportunities for Nurses to Lead

There are opportunities for nurses to facilitate delivery of care to patients with NF1 PN, to help improve diagnosis and treatment. The following are suggested nursing practices for ensuring continuity of care during the COVID-19 era and beyond:

Education and Support

Multidisciplinary Care Coordination

The Way Forward

Coupled with the COVID-19 pandemic and logistical challenges for accessing care, a patient’s journey with NF1 PN may be challenging. On top of this, many patients and families are encountering barriers to access healthcare services. In this new normal, nurses can play a vital role in safeguarding patients from COVID-19 infection while supporting access to care, leading to timely diagnosis and treatment.

IMPORTANT SAFETY INFORMATION

Cardiomyopathy. A decrease in left ventricular ejection fraction (LVEF) ≥10% below baseline occurred in 23% of 74 pediatric patients who received Koselugo in SPRINT. Four percent of patients experienced decreased LVEF below the institutional lower limit of normal (LLN). Grade 3 decreased LVEF occurred in one patient and resulted in dose reduction. All patients with decreased LVEF were asymptomatic and identified during routine echocardiography. Decreased LVEF resolved in 71% of these patients. Decreased LVEF resulting in permanent discontinuation of Koselugo occurred in a pediatric population with NF1 in an expanded access program. The safety of Koselugo has not been established in patients with a history of impaired LVEF or a baseline ejection fraction that is below the institutional LLN.

Assess ejection fraction by echocardiogram prior to initiating treatment, every 3 months during the first year of treatment, every 6 months thereafter, and as clinically indicated. Withhold, reduce dose, or permanently discontinue Koselugo based on severity of adverse reaction. In patients who interrupt Koselugo for decreased LVEF, obtain an echocardiogram or a cardiac MRI every 3 to 6 weeks. Upon resolution of decreased LVEF, obtain an echocardiogram or a cardiac MRI every 2 to 3 months

Ocular Toxicity. Blurred vision, photophobia, cataracts, and ocular hypertension occurred in 15% of 74 pediatric patients receiving Koselugo in SPRINT. Blurred vision resulted in dose interruption in 2.7% of patients. Ocular toxicity resolved in

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82% of 11 patients. Retinal pigment epithelial detachment (RPED) occurred in the pediatric population during treatment with single agent Koselugo and resulted in permanent discontinuation.

Conduct ophthalmic assessments prior to initiating Koselugo, at regular intervals during treatment, and for new or worsening visual changes. Permanently discontinue Koselugo in patients with retinal vein occlusion (RVO). Withhold Koselugo in patients with RPED, conduct ophthalmic assessments every 3 weeks until resolution, and resume Koselugo at a reduced dose. For other ocular toxicities, withhold, reduce dose, or permanently discontinue Koselugo based on severity of adverse reaction.

Gastrointestinal Toxicity. Diarrhea occurred in 77% of 74 pediatric patients who received Koselugo in SPRINT, including Grade 3 in 15% of patients. Diarrhea resulting in permanent discontinuation occurred in 1.4% of patients. Diarrhea resulting in dose interruption or dose reduction occurred in 15% and 1.4% of patients, respectively. The median time to first onset of diarrhea was 17 days, and the median duration was 2 days.

Advise patients to start an anti-diarrheal agent (eg, loperamide) and to increase fluid intake immediately after the first episode of diarrhea. Withhold, reduce dose, or permanently discontinue Koselugo based on severity of adverse reaction.

Skin Toxicity. Rash occurred in 91% of 74 pediatric patients who received Koselugo in SPRINT. The most frequent rashes included dermatitis acneiform (54%), maculopapular rash (39%), and eczema (28%). Grade 3 rash occurred in 8% of patients. Rash resulted in dose interruption in 11% of patients and dose reduction in 4% of patients. Monitor for severe skin rashes. Withhold, reduce dose, or permanently discontinue Koselugo based on severity of adverse reaction.

Increased Creatine Phosphokinase (CPK). Increased CPK occurred in 76% of 74 pediatric patients who received Koselugo in SPRINT, including Grade 3 or 4 in 9% of patients. Increased CPK resulted in dose reduction in 7% of patients. Increased CPK concurrent with myalgia occurred in 8% of patients, including one patient who permanently discontinued Koselugo for myalgia.

Obtain serum CPK prior to initiating Koselugo, periodically during treatment, and as clinically indicated. If increased CPK occurs, evaluate patients for rhabdomyolysis or other causes. Withhold, reduce dose, or permanently discontinue Koselugo based on severity of adverse reaction.

Increased Levels of Vitamin E and Risk of Bleeding. Koselugo capsules contain vitamin E (10 mg capsules contain 32 mg vitamin E as the excipient, D-alpha-tocopheryl polyethylene glycol 1000 succinate [TPGS], while Koselugo 25 mg capsules contain 36 mg vitamin E as TPGS). Vitamin E can inhibit platelet aggregation and antagonize vitamin K-dependent clotting factors. Daily vitamin E intake that exceeds the recommended or safe limits may increase the risk of bleeding. Supplemental vitamin E is not recommended if daily vitamin E intake (including the amount of vitamin E in Koselugo and supplement) will exceed the recommended or safe limits.

An increased risk of bleeding may occur in patients who are coadministered vitamin-K antagonists or anti-platelet antagonists with Koselugo. Monitor for bleeding in these patients and increase international normalized ratio (INR) monitoring in patients taking a vitamin-K antagonist. Perform anticoagulant assessments more frequently and adjust the dose of vitamin-K antagonists or anti-platelet agents as appropriate.

Embryo-Fetal Toxicity. Based on findings from animal studies, Koselugo can cause fetal harm when administered to a pregnant woman. In animal studies, administration of selumetinib to mice during organogenesis caused reduced fetal weight, adverse structural defects, and effects on embryo-fetal survival at approximate exposures >5 times the human exposure at the clinical dose of 25 mg/m ² twice daily. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Koselugo and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Koselugo and for 1 week after the last dose.

Breastfeeding. Due to the potential for adverse reactions in a breastfed child, advise women not to breastfeed during treatment with Koselugo and for 1 week after the last dose.

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Concomitant use of Koselugo with a strong or moderate CYP3A4 inhibitor or fluconazole  increased selumetinib plasma concentrations, which may increase the risk of adverse reactions. Avoid coadministration of strong or moderate CYP3A4 inhibitors or fluconazole with Koselugo. If coadministration with strong or moderate CYP3A4 inhibitors or fluconazole cannot be avoided, reduce Koselugo dosage.

Concomitant use of Koselugo with a strong or moderate CYP3A4 inducer  decreased selumetinib plasma concentrations, which may reduce Koselugo efficacy. Avoid concomitant use of strong or moderate CYP3A4 inducers with Koselugo.

The most common adverse reactions  ≥40% are: vomiting, rash (all), abdominal pain, diarrhea, nausea, dry skin, musculoskeletal pain, fatigue, pyrexia, acneiform rash, stomatitis, headache, paronychia, and pruritus.

INDICATION
Koselugo is indicated for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).

Please see complete Prescribing Information, including Patient Information.

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Koselugo is a registered trademark of the AstraZeneca group of companies.

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