Pharmacotherapeutic group: other peripherally acting muscle relaxants, ATC code: M03AX01
Mechanism of action
The primary pharmacodynamic effect of botulinum toxin type A is chemical denervation of the treated muscle, resulting in a measurable decrease in the compound muscle action potential. This causes a localised reduction in muscle activity.
Botulinum toxin type A is a muscle relaxant that temporarily weakens muscle activity. Following injection, botulinum toxin type A acts by blocking the transport of the neurotransmitter acetylcholine at the neuromuscular junctions located between the nerve endings and the muscle fibre. The mechanism of action involves 4 main phases. For the effect to occur, all of these phases must proceed correctly. The consequence is cessation of contractions in the target muscles. The effect persists until the junction recovers and muscle activity is restored.
Clinical efficacy and safety
In 2 pivotal studies, a total of 372 patients with moderate to severe glabellar lines were treated, 250 at the recommended dose of 50 Speywood units and 122 with placebo.
Most patients subjectively reported an effect within 2 to 3 days, including 23% of patients who reported an effect within 1 day.
One month after injection, the responder rate according to the investigator assessment was statistically significantly higher in patients treated with Alluzience compared with placebo (primary endpoint), as well as at all other time points from 8 days to 6 months (Table 2).
Table 2: Investigator Live Assessment at maximum frown – response rate (%) at various time points
Post-injection visit
Alluzience (n=250)
Placebo (n=122)
8 days
80.0%
2.5%
1 month
87.6%
2.5%
2 months
76.8%
1.7%
3 months
57.6%
1.7%
4 months
36.3%
1.8%
Post-injection visit
Alluzience (n=250)
Placebo (n=122)
5 months
17.5%
0.9%
6 months
10.0%
0.9%
Note: A responder is defined as a person who has a moderate or severe severity grade at baseline and a none or mild severity grade at the given visit.
The response rate, the primary efficacy endpoint at Day 29, was statistically significantly different from placebo (p <0.0001). Response rates at other time points were nominally different from placebo (p-values ranging from ≤0.0001 to 0.0008).
The proportion of responders according to patient self-assessment was higher in patients treated with Alluzience compared with placebo at all time points from 8 days to 6 months (Table 3).
Table 3: Patient Self-Assessment – response rate (%) at various time points
Post-injection visit
Alluzience (n=250)
Placebo (n=122)
8 days
66.0%
4.9%
1 month
76.8%
5.7%
2 months
72.4%
2.5%
3 months
48.8%
3.4%
4 months
32.7%
4.3%
5 months
23.1%
4.3%
6 months
15.1%
2.6%
Note: A responder is defined as a person who has a moderate or severe severity grade at baseline and a none or mild severity grade at the given visit.
Response rates were nominally different from placebo, with p-values ≤0.0001 at all time points.
The level of patient satisfaction 1 month after injection showed that 85.2% of patients after Alluzience use were either satisfied or very satisfied, compared with 9% of patients treated with placebo.
Aesthetic and psychological improvement was monitored using FACE-Q scales. For the overall facial appearance scale (which includes subject ratings for facial symmetry, end-of-day appearance, facial freshness, rested appearance, appearance upon waking, and appearance under bright light) and the psychological well-being scale (which includes subject ratings for feeling good about oneself, self-acceptance, feeling comfortable with oneself, feeling that one likes oneself, feeling happy, feeling attractive, and feeling self-confident) one month after injection, patients treated with Alluzience showed improvement in scores for each of these scales compared with patients treated with placebo (nominal p <0.0001).
In a long-term, open-label, phase III study lasting 12 months, a total of 595 patients received up to 5 treatment cycles with Alluzience. According to investigator assessment, patient assessment, patient satisfaction, and FACE-Q questionnaires, efficacy was maintained over the 12-month period.
The responder rate at maximum frown as assessed by the evaluator 1 month after injection persisted across repeated injection cycles (between 82.2% and 87.8%). The corresponding rates 3 months after injection ranged between 45.3% and 56.8% over 5 treatment cycles.
Patients (595 in total) who received Alluzience over 12 months were tested for antibody formation. No patients tested positive for toxin-neutralising antibodies.
⚠️ Warnings
Care should be taken to ensure that Alluzience is not injected into a blood vessel.
Injection of Alluzience is not recommended in patients with a history of dysphagia and aspiration.
Very rarely, adverse reactions probably related to the spread of the toxin to sites distant from the injection site have been reported with botulinum toxin. Swallowing and breathing disorders are serious and may cause death.
Very rarely, deaths have been reported following treatment with botulinum toxin type A or B, occasionally in association with dysphagia, pneumopathy (including dyspnoea, respiratory failure, respiratory arrest, and other symptoms) and/or in patients with significant asthenia.
Patients should be advised to seek immediate medical attention if they experience difficulties with swallowing, speech, or breathing.
Alluzience should be used with caution in patients at risk of, or with clinical signs of, significant neuromuscular transmission disorders. Such patients may have increased sensitivity to agents such as botulinum toxin, and excessive muscle weakness may follow treatment.
Before administering Alluzience, it is essential to examine the patient's facial anatomy. Facial asymmetry, ptosis, excessive dermatochalasis, scarring, and any changes in anatomy as a result of prior surgical intervention should be taken into account.
Cases of dry eyes have been reported with the use of Alluzience in the area around the eyes (see section 4.8). It is important to pay attention to this adverse effect, as dry eyes may predispose to corneal disorders. Protective drops, ointment, eye patching, or other measures to protect the eye may be necessary for the prevention of corneal disorders.
The recommended dose and frequency of administration of Alluzience must not be exceeded.
Patients treated at the recommended dose may experience exaggerated muscle weakness.
Caution is required if Alluzience is used in the presence of inflammation at the proposed injection site or if the target muscle(s) exhibit(s) excessive weakness or atrophy. Cases of muscle atrophy have been reported following the use of botulinum toxin (see section 4.8).
As with all intramuscular injections, the use of Alluzience is not recommended in patients with prolonged bleeding time.
A single vial of Alluzience must be used for the treatment of one patient during a single session.
Any remaining unused product must be disposed of as described in section 6.6. Special care should be taken in the inactivation and disposal of any remaining unused solution (see section 6.6).
Antibody formation
Injections at more frequent intervals or at higher doses may increase the risk of formation of neutralising antibodies to botulinum toxin. Clinically, the formation of neutralising antibodies may reduce the efficacy of subsequent treatment.
Traceability
In order to improve the traceability of biological medicinal products, the name of the administered product and the batch number should be clearly recorded.
Sodium content
This medicinal product contains less than 1 mmol (23 mg) sodium per vial containing 125 units, i.e. it is essentially 'sodium-free'.
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