On 26 August 2022 the President of the Agency for Health Technology Assessment and Tariff System issued the following recommendation:
Recommendation No. 85/2022 of 26 August 2022 of the President of the Agency for Health Technology Assessment and Tariff System on the evaluation of foodstuff for particular nutritional uses Milupa Basic-P for the indications: methylmalonic aciduria, isovaleric aciduria, propionic aciduria, glutaric aciduria, citrulinaemia, CPS1 deficiency, type II hyperammonemia (OTC deficiency), maple syrup disease, Wolf-Hirschhorn syndrome, hypoglycaemia-hyperammonemia syndrome.
The President of the Agency recommends issuing approvals for the reimbursement of Milupa Basic-P foodstuff for particular nutritional uses for the following indications: methylmalonic aciduria, isovaleric aciduria, propionic aciduria, glutaric aciduria, citrullinemia, carbamoyl phosphate synthetase 1 (CPS1) deficiency, maple syrup urine disease, hyperammonemia type 2.
The President of the Agency does not recommend issuing approvals for the reimbursement of Milupa Basic-P foodstuff for particular nutritional uses for the following indications: hypoglycemia–hyperammonemia syndrome, Wolf-Hirschhorn syndrome.
Grounds for the recommendation
The above-mentioned indications are classified as rare diseases. These are mostly genetically determined metabolic disorders for which the identified guidelines recommend a low-protein diet combined with individualized management depending on the diagnosed disease and patient condition, e.g. supplementation of appropriate amino acids, vitamin B12, administering nitrogen-removing drugs.
Wolf-Hirschhorn syndrome is a multiple malformation syndrome and, as indicated by the clinical expert, its treatment is only symptomatic. As it does not involve protein metabolism disorders, the use of a product to support a low-protein diet by the patients is unjustified.
In recommendation no. 25/2019, the President of the Agency recommended issuing approvals for the reimbursement of Basic-P foodstuff for particular nutritional uses for in the following indications: methylmalonic aciduria, isovaleric aciduria, propionic aciduria, glutaric aciduria, citrullinemia, carbamoyl phosphate synthetase 1 (CPS1) deficiency, maple syrup urine disease, hyperammonemia type 2, hypoglycemia–hyperammonemia syndrome. At the same time, issuing approvals for the reimbursement of Basic-P in Wolf-Hirschhorn syndrome was considered unjustified.
No clinical performance and safety studies were found on the use of ready-to-use protein-free products with a composition similar to Milupa Basic-P for the analyzed indications that were published after 2019, that is, after the recommendation of the President of the Agency no. 25/2019 was issued.
Therefore, the clinical analysis included the case study by Kowalik (2021) concerning a 31-year-old female with methylmalonic aciduria who used Milupa Basic-P during pregnancy. The patient was regularly monitored, which allowed adjusting therapy on an ongoing basis needs and maintaining metabolic control. No clinical or biochemical symptoms of metabolic decompensation occurred during pregnancy. The woman gave birth to a healthy baby girl at 38 weeks of gestation by cesarean section. No metabolic decompensation was reported in the perinatal period, although methylmalonic aciduria increased do 31.1 µmol/L as measured by a dried blood spot (DBS) test 2 weeks before delivery.
It should be noted that in the case of rare metabolic disorders whose treatment is based on individualized dietary management, the probability of high-quality clinical research being conducted is low. The obtained results suggesting a clinical effect of the products would involve multiple uncertainties and would be based on small groups of patients.
Furthermore, the clinical expert indicates that if appropriate treatment is quickly initiated, the risk of intoxication syndrome or coma due to hyperammonemia can be reduced. Therefore, it is critical to provide patients with permanent access to appropriate foodstuffs for particular nutritional uses, whether in cases of newly diagnosed congenital metabolic disorders or for continued therapy.
According to the Ministry of Health data, Milupa Basic-P was not imported for patients with hypoglycemia–hyperammonemia syndrome and Wolf-Hirschhorn syndrome in 2021.
Due to the limited size of the current population and the price of the product, the expected burden for the public payer budget associated with the reimbursement of the product under assessment is insignificant.
Taking into account the position of the Transparency Council and the above arguments, especially the significance of the clinical condition and the ability to meet the patients’ health needs, continuing the reimbursement of the proposed technology is considered justified for patients with methylmalonic aciduria, isovaleric aciduria, propionic aciduria, glutaric aciduria, citrullinemia, carbamoyl phosphate synthetase 1 (CPS1) deficiency, maple syrup urine disease and hyperammonemia type 2.