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Aqneursa (levacetylleucine)

Ataxia-telangiectasia

Also known as IB1001
Manufacturer
IntraBio
Last updated
206 sources

Product information and disease descriptionPlace of product in therapyDisease description

Long-term morbidity

14 evidence topics · 20 sources

Cancer incidence: French national registry

“In this large retrospective cohort, 69 patients with cancers (24.5%) were identified among 279 patients with AT.” (opens the source at this quote in a new tab)

“Eight patients developed acute leukemias (including four T-cell acute lymphoblastic leukemias), 12 developed Hodgkin lymphoma (HL), 38 developed non-Hodgkin lymphoma (NHL), three developed T-cell prolymphocytic leukemia (T-PLL), and eight developed carcinoma at a median age of 8.3, 10.6, 9.7, 24.2, and 31.4 years, respectively (P < .001).” (opens the source at this quote in a new tab)

“Immunodeficiency was associated with increased risk of cancer.” (opens the source at this quote in a new tab)

Cancer incidence: Johns Hopkins Ataxia Telangiectasia Clinical Center cohort

“Eighty-four (16.5%) of 508 individuals were diagnosed with a primary cancer, of whom 62 (74%) were hematologic in origin and 22 (26%) were solid-organ cancers. The cumulative incidence of cancer was 29% by age 35 years.” (opens the source at this quote in a new tab)

“Non–Hodgkin lymphoma occurred most frequently (n = 39), whereas solid cancers disproportionately affected those 18 years and older (n = 22).” (opens the source at this quote in a new tab)

Childhood cancer risk: German register-based cohort

“Among the 160 patients with AT, we observed 19 cases of childhood cancer (15 cases of lymphoma, three cases of leukemia, and one case of medulloblastoma) versus 0.32 expected. This corresponds to a 56-fold increased risk (SIR = 56; 95% CI, 33 to 88).” (opens the source at this quote in a new tab)

“Approximately 11% of patients with FA and 14% of patients with AT develop cancer by age 18 years.” (opens the source at this quote in a new tab)

Tumor type, residual ATM kinase activity, and breast cancer risk

“From a total of 296 consecutive genetically confirmed A-T patients from the British Isles and the Netherlands, we identified 66 patients who developed a malignant tumour; 47 lymphoid tumours and 19 non-lymphoid tumours were diagnosed.” (opens the source at this quote in a new tab)

“In addition, the presence of eight breast cancers in A-T patients, a 30-fold increased risk, establishes breast cancer as part of the A-T phenotype.” (opens the source at this quote in a new tab)

“This gives a standardised mortality ratio of 31.1 (with a wide 95% CI=14.4–74.7) equivalent to a cumulative risk of breast cancer diagnosis by the age of 50 years of 45% (95% CI=24–76%)” (opens the source at this quote in a new tab)

Outcomes of hematological malignancies in children and young adults

“In this multinational, observational study we report 202 patients aged ≤25 years with A-T and hematological malignancies from 25 countries.” (opens the source at this quote in a new tab)

“Four-year overall survival and event-free survival (EFS) were 50.8% (95% confidence interval [CI], 43.6-59.1) and 47.9% (95% CI 40.8-56.2), respectively.” (opens the source at this quote in a new tab)

“The major cause of treatment failure was treatment-related mortality (TRM) with a four-year cumulative incidence of 25.9% (95% CI, 19.5-32.4).” (opens the source at this quote in a new tab)

Excess cancer incidence in a historical United States cohort

“There were 52 primary cancers, representing a 61-fold cancer excess for white probands and a 184-fold excess for black probands.” (opens the source at this quote in a new tab)

Cancer in variant A-T

“Fourteen patients have been diagnosed with a malignancy.” (opens the source at this quote in a new tab)

“Missense mutations were associated with milder neurological disease severity, but with a higher risk of malignancy, compared to leaky splice site mutations.” (opens the source at this quote in a new tab)

Chronic lung disease: bronchiectasis and interstitial lung disease

“The medical records of 97 patients with A-T and chronic lung disease were reviewed. Interstitial lung disease (ILD) was specifically diagnosed in 25 of 97 patients.” (opens the source at this quote in a new tab)

“Nineteen of these 25 patients with ILD died within 24 months of the onset of their ILD, and of 7 patients treated with corticosteroids, 5 are still alive.” (opens the source at this quote in a new tab)

“Occurrence of recurrent sinopulmonary infections (n=45) and bronchiectasis (n=22) were found to be more common in patients with impaired immunological parameters (P=0.029 and P=0.023, respectively).” (opens the source at this quote in a new tab)

“Lung disease is common in patients with A-T and often progresses with age and neurological decline. Diseases of the respiratory system cause significant morbidity and are a frequent cause of death in the A-T population.” (opens the source at this quote in a new tab)

Lung function

“The mean forced vital capacity % predicted (FVC %) in the population was 56.6 ± 20.0.” (opens the source at this quote in a new tab)

“No significant change in FVC % was found in a subset of subjects (n = 25) who underwent pulmonary function testing on two or more occasions over an average of 2 years.” (opens the source at this quote in a new tab)

“FVC declined from 67 ± 8 while walking to 19 ± 6 %predicted values.” (opens the source at this quote in a new tab)

Dysphagia, growth failure, and nutritional decline

“Oropharyngeal dysphagia is common and appears to be progressive in patients with ataxia-telangiectasia. Older patients also have a higher incidence of poorer nutritional status.” (opens the source at this quote in a new tab)

“101 children (51 girls) had 222 measurements (32 once, 32 twice, 24 thrice) between 2009 and 2016.” (opens the source at this quote in a new tab)

“35/101 children had weight Z-scores below -2 on at least one occasion. Weight, height and BMI Z-scores declined over time. Decline was most obvious after 8 years of age. 14/101 (14%) children had a PEG, with longitudinal data available for 12.” (opens the source at this quote in a new tab)

“The distribution of patients according to nutritional status by age group revealed an over-time increase in the proportion of patients with severe thinness (p = 0.016). High glucose and triglyceride levels were observed in 9.5% and 23.6% of patients, respectively.” (opens the source at this quote in a new tab)

Diabetes and insulin resistance

“Seven out of 39 (17.9%) patients suffered from diabetes.” (opens the source at this quote in a new tab)

“Diabetes is a common finding in older A-T patients and often starts in puberty.” (opens the source at this quote in a new tab)

“Three patients developed type 2 diabetes in young adulthood and nine patients (64%) had a history of elevated liver function tests.” (opens the source at this quote in a new tab)

Liver disease

“For analysis, patients were divided into two age groups (Group 1: <12 years; group 2: ≥12 years).” (opens the source at this quote in a new tab)

“Ultrasound revealed hepatic steatosis in 11/19 (57.9%) patients in group 2.” (opens the source at this quote in a new tab)

“Liver disease is present in the majority of older A-T patients.” (opens the source at this quote in a new tab)

Loss of ambulation, neuropathy, and immobility

“Polyneuropathy, determined by clinical examination was present in 9/13 (69%) and by neurophysiological studies in 3/5 (60%), cognitive impairment in 8/14 (53%), wheelchair use in 11/14 (79%), and cerebellar atrophy in 9/11 (82%) patients.” (opens the source at this quote in a new tab)

“All patients with classic A–T beyond the age of 30 years were wheelchair-bound and dependent on others in activities of daily living (ADL). As a result of immobilization most patients developed pressure sores and had constipation.” (opens the source at this quote in a new tab)

Orthopedic and age-related complications

“Acquired deformity of the feet is common in people with A-T (unpublished observations) and compounds the difficulty individuals have with walking due to impaired coordination.” (opens the source at this quote in a new tab)

“Certain problems occur with an unexpectedly high frequency in patients with A-T who survive into their twenties and beyond.” (opens the source at this quote in a new tab)