SAIZEN (somatropine) - Hormone de croissance

 Key points

Favourable opinion for reimbursement in:

• Growth disturbance (current height SDS <-3 and parental adjusted height SDS <-1) in short children born small for gestational age (SGA) with a birth weight and/or length below -2 SD, who failed to show catch-up growth (HV SDS <0 during the last year) by 4 years of age or later,
• Replacement therapy in adults with pronounced growth hormone deficiency as diagnosed by a single dynamic test for growth hormone deficiency.

In growth failure in children born small for gestational age, the clinical benefit is now moderate, whereas previously it was low.

What therapeutic improvement?

No clinical added value in the therapeutic strategy.

Role in the care pathway?

Somatropin may only be used within the strict indications of the marketing authorisation (MA). The decision to treat should be based on the criteria of the clinical benefit sheet for each indication and the dosages should always be respected. However, the somatropin dose may be adjusted based on growth, clinical safety and IGF-1 concentrations.

The benefit of treatment should be regularly reassessed.

Role of the medicinal product in the care pathway

Growth failure in children born small for gestational age

Any organic causes or treatments that could explain growth failure should be investigated and ruled out before starting treatment with rhGH. Growth stimulation in children may only be performed before the epiphyses are fused. Experience in initiating treatment in small for gestational age children near onset of puberty is limited. It is therefore not recommended to initiate treatment near onset of puberty. The criteria for initiation of rhGH treatment that must all be met are:

• height warranting initiation of treatment ≤-3 SD for chronological age;
• birth weight and/or length below -2 SD for gestational age;
• children having failed to show catch-up growth (HV SDS <0 during the last year) by 4 years of age or later;
• height <-1 SD compared to parental adjusted height.

Children treated with rhGH will have a follow-up consultation every three months, including a consultation with a specialist once per year to assess the efficacy of this treatment and the benefit of continuing it. The treatment discontinuation criteria are:

• onset or progression of a tumour disease process;
• after the first year of treatment, a height velocity <+1 SD;
• height velocity < 2 cm/year;
• fusing of epiphyses on X-rays.

In children, treatment should be stopped after 1 year of treatment in non-responders (height velocity < 2 cm/year). In all cases, treatment with somatropin should be reassessed after 1 to 2 years of treatment, when follow-up of growth is sufficient.

Documented pronounced growth hormone deficiency in adults

Testing for GH deficiency in adults should only be performed in patients with a condition suggestive of a growth hormone deficiency and who:

• either have hypothalamic or pituitary disease, treated surgically or otherwise;
• or have undergone brain radiotherapy;
• or had a growth hormone deficiency in childhood.

There is no data justifying the initiation of rhGH treatment in adults over 60 years of age. Replacement therapy for other hormone deficiencies must have been adjusted and be stable for three months before investigating for and treating a growth hormone deficiency. Treatment with rhGH is justified if:

• the deficiency is biologically demonstrated by appropriate tests; and
• the patient has a marked deterioration in quality of life (fatigability, difficulty on exertion) as well as a change in body composition (abdominal adiposity with an increased waist-to-hip ratio).

The objective of treatment is to obtain a maximum benefit while limiting adverse effects. It is recommended to initiate treatment at low dosages in the region of 0.15 to 0.30 mg/day. The objective of treatment is to obtain an insulin-like growth factor I (IGF1) concentration that is normal for gender and age. At the start of treatment, patients should be assessed every 1 to 2 months; the rhGH dose should be adjusted on the basis of clinical tolerance and IGF1 concentrations. The lowest effective dose must be sought. The initiation of treatment with low doses along with a gradual increase every 1 to 2 months helps limit the occurrence of adverse effects. Depending on the results and tolerance, the dosage may be increased within an interval of 3 to 6 months without exceeding the maximum doses recommended by the MA. Patients must be informed about the adverse effects (see SPC). In the event of persistent adverse effects, the dosages should first be reduced, then treatment discontinuation should be discussed.

Somatropin is contraindicated in the event of an active tumour disease process. In the event of a history of tumour disease, in the absence of a precise diagnosis of the tumour or if the tumour is clinically known to recur frequently, it is not advisable to initiate treatment with rhGH.

In other cases of tumour history and before initiating replacement therapy, it is necessary to ensure the absence of renewed activity of the process by means of a monitoring period before treatment initiation, the duration of which should be determined with the oncologists and/or neurosurgeons and using MRI imaging.

Follow-up of treatment.

There is still no validated endpoint for assessing the efficacy of rhGH in adults. The improvement is primarily subjective (improvement in quality of life, reduced fatigability, etc.). However, patients treated with GH should be regularly monitored, with weight, waist/hip circumference and blood pressure being recorded every one to two months until optimal rhGH doses are stabilised. After that, follow-up visits can be six-monthly. An assessment of quality of life, as well as body composition parameters, comparing these to the data from the assessment before treatment, enables a decision to be taken concerning the continuation of the treatment. When it is decided to use GH to treat a deficiency secondary to an intracranial tumour, patients must be monitored regularly to detect any progression or recurrence. Any tumour recurrence or progression requires the discontinuation of treatment.

Treatment compliance and the results of replacement therapy for associated anterior pituitary deficiencies should be verified at least once per year and will also be taken into account to assess the benefit of continuing treatment.

In adults, there is no validated endpoint for assessing the efficacy of somatropin. The improvement is primarily subjective (impact on quality of life, reduced fatigability, etc.).