Effective acne therapy still remains an urgent problem, which is associated with a significant prevalence of the disease, especially among adolescents and young adults. At the round table “Key moments of successful therapy with isotretinoin: expert opinion”, organized with the support of the company “Yadran” in the framework of the XVI All-Russian Congress of Dermatovenereologists and Cosmetologists (Moscow, June 16, 2016), leading Russian experts – Head of the Department of Skin and Venereal Diseases of the Military – medical academy. CM. Kirov, Honored Worker of Science of the Russian Federation, Doctor of Medical Sciences, Professor Aleksey Viktorovich SAMTSOV, Professor of the Department of Dermatovenereology of the First St. Petersburg State Medical University. Academician I.P. Pavlova, MD Elena Roaldovna ARAVIYSKAYA, Professor, Department of Skin and Venereal Diseases, Saratov State Medical University, MD Andrey Leonidovich BAKULEV, Head of the Scientific Clinical Department of Dermatology of the Ural Research Institute of Dermatovenereology and Immunopathology, Doctor of Medical Sciences, Professor Muza Mikhailovna KOKHAN – discussed modern approaches to acne therapy, in particular, the possibility of using https://www.japan-zone.com/news/buy-accutane-online-usa/ (using the drug Aknekutan as an example), and conditions, the observance of which will ensure the maximum effect of the therapy and long-term remission of the disease.
Isotretinoin preparations for systemic acne therapy remain the most effective in the treatment of this disease and are used more and more widely by both foreign and domestic specialists every year.
As Professor A.L. Bakulev, isotretinoin went through a difficult path – from the denial of its positive properties to their recognition. To date, isotretinoin is included in modern domestic and international recommendations as a first-line drug for the treatment of severe and resistant forms of acne.
According to the latest American Academy of Dermatology (AAD)1 acne guidelines, isotretinoin is indicated for the treatment of severe nodular acne, moderate acne that is resistant to other treatments, and acne that is at high risk of scarring. , or acne, accompanied by psychosocial distress.
According to Professor E.R. The Arabian, European approach to the treatment of this disease will be reflected in the new recommendations of the European Academy of Dermatology and Venereology (European Academy of Dermatology and Venereology – EADV)2, which will be published in 2016. The principles of therapy laid down in them are similar to the principles of therapy presented in the AAD recommendations , as well as in the Russian clinical guidelines for acne therapy.
In addition, E.R. Arabian introduced the audience to one of the latest articles on acne treatment, which is being prepared for publication in the journal EADV. It is dedicated to new practical recommendations for acne therapy. This article contains simple and easy-to-use algorithms for the treatment of this disease, which, among other things, help to understand why the prescribed treatment does not always achieve the expected result. In particular, data are provided that in case of failure of acne therapy using systemic isotretinoin, it is necessary to assess the severity of the disease, check the dose of isotretinoin.
Professor A.V. Samtsov drew the attention of the audience to the fact that the choice of the optimal dose of isotretinoin still remains an urgent problem.
The AAD guidelines state that the dose should be 0.5 mg/kg for the first month of therapy, then increased to 1 mg/kg twice daily1. The duration of therapy is 15-20 weeks. Heading dose – not less than 120 mg / kg, but in recent years there has been a tendency to increase it.
In addition, new in the latest AAD recommendations is the possibility of using reduced daily doses of isotretinoin in moderate acne (in the range of 0.25–0.4 mg/kg) in order to reduce the risk of side effects, as well as reduce the course dose of isotretinoin. In this case, the exact cumulative doses in this case are not given. The speaker emphasized that the AAD does not recommend the use of intermittent regimens due to the high risk of relapse and low efficacy.
Professor M.M. Kohan supported this provision of the recommendations: “The use of microdoses, intermittent treatment regimens is a thing of the past.” However, in practice, unfortunately, for many years now one has to deal with the incorrect prescription of isotretinoin in ultra-low doses, as well as the use of intermittent regimens, when isotretinoin is taken not every day, but only sometimes – once or twice a week. MM. Kohan emphasized that clinical studies have shown a short-term effect of this approach: after improvement, relapse quickly occurs. The use of isotretinoin should be stable and monotonous. The patient must know what dose to take at what time. The intermittent regimen of therapy, according to the speaker, discourages patients – they often forget to take the drug, and the pharmacodynamics of isotretinoin is such that it does not last long at therapeutic concentrations. As a result, the full effect on the sebaceous gland is not achieved.
The position of colleagues on this issue was supported by Professor E.R. Arabian. She explained that the accumulation of isotretinoin is not molecular, but physiological, therefore, for an effective effect on the sebaceous gland, a sufficient period of time is needed to take it. This is confirmed by the Russian experience of using isotretinoin. Thus, according to the results of one of the largest studies of isotretinoin in Russia, which included 1349 patients aged 14–63 years with severe acne, who were prescribed isotretinoin at an average dose of 0.5–1 mg/kg, only by the 28th week of therapy in more than a third (37.1%) of patients had regression of lesions by 90% or more (Fig. 1)3.
Professor A.V. Samtsov clarified that in the treatment with isotretinoin, the form of the drug is also important. In particular, in 2001, an innovative LIDOSE technology was patented for isotretinoin in Belgium, which increases its bioavailability compared to conventional isotretinoin preparations. In Russia, the only isotretinoin drug produced using LIDOSE technology is Aknekutan.
The results of studies of isotretinoin, produced using LIDOSE technology, allowed the US Food and Drug Administration and Health Canada in 2012 to approve the use of this technology. In particular, it has been noted that isotretinoin in the form of capsules containing liquid lipid excipients is indicated for the treatment of severe, nodular-conglobate and other inflammatory acne, including persistent ones.
A.V. Samtsov explained what the essence of LIDOSE technology is. Two substances are added to isotretinoin that increase the absorption of isotretinoin in the digestive tract, as a result of which its bioavailability increases by 20%. Thanks to this, it is possible to reduce both single and course doses of isotretinoin by 20% while maintaining the therapeutic effect. As a result, the risk of side effects is reduced, which is very important in the treatment of patients with acne.
The recommended daily dose of Aknekutan is 0.4–0.8 mg/kg, the course dose is 100–120 mg/kg (Table 1).
On the basis of the Military Medical Academy. CM. Kirov, a study was conducted on the efficacy and safety of Aknekutan in patients with moderate and severe acne. The age of the participants is 15–29 years. For five to seven months, patients with moderate acne (n = 38) received the drug at a dose of 0.4–0.6 mg/kg per day, patients with severe acne (n = 18) at a dose of 0.6– 0.8 mg/kg per day. The cumulative dose of Acnecutane was 100–120 mg/kg. The results of the study demonstrated the high efficacy and safety of therapy. Thus, by the 150th day, 100% clinical remission was achieved (Table 2).
This was manifested by a reduction in inflammatory (nodules, papules, pustules) and non-inflammatory (open and closed comedones) elements of the rash (Fig. 2). Against the background of the therapy, such undesirable phenomena as dry skin and cheilitis were noted.
Professor M.M. Kokhan presented to the roundtable participants the results of a study of the clinical efficacy and safety of Aknekutan therapy in patients with acne of varying severity, conducted by specialists from the Ural Research Institute of Dermatovenereology and Immunopathology. All patients (n = 32) were divided into three groups according to the severity of the skin process (A, B, C).
Group A patients suffering from moderate acne vulgaris received therapy with Aknekutan at a starting dose of 0.2–0.25 mg/kg per day. Group B patients with severe acne were prescribed Aknekutan at a dose of 0.6–0.8 mg/kg per day. Group B patients – with acne conglobata – at a starting dose of 0.8–1.2 mg / kg per day. Participants took the initial starting dose for 8-12 weeks, when regression was achieved, the dose of the drug was reduced by 10-20% every four weeks.
In patients with moderate acne, complete clinical remission was achieved by the 12–18th week of Aknekutan therapy at an average cumulative dose of at least 80 mg/kg.
In patients with severe acne, a complete clinical remission of the skin process occurred by the 20–24th week, the cumulative course dose of the drug was 80–115 mg/kg (Fig. 3). Patients with acne conglobate achieved clinical remission by week 24–32 at a cumulative course dose of 90–125 mg/kg.
Professor A.L. Bakulev noted that sometimes the use of isotretinoin in standard doses can cause difficulties, for example, in the presence of concomitant pathology in a patient, a phobia of treatment on the part of the patient or his relatives. In this regard, in some cases, mainly in the presence of medical indications, the daily dose of isotretinoin can be reduced, but the duration of treatment in such patients is significantly increased, due to the need to set the recommended course dose.
As an illustration, the results of a study conducted at the Saratov Medical University were presented. Patients (n = 36) were divided into two equal groups. In the first group, the standard regimen of treatment with Aknekutan was used, in the second group, the regimen of reduced daily doses.
At the same time, patients of the second group received Aknekutan in a high dose – 1 mg / kg per day only during the first month, then it decreased to 16 mg (one capsule) per day. Patients received this dose for a year.
Both treatment regimens made it possible to reach the course cumulative dose of the drug: in the first group – at the 27th week, in the second – at the 52nd week (Fig. 4). In both cases, significant side effects were not observed, however, in the second group, the tolerability of treatment during the entire period of therapy was better.
Professor A.V. Samtsov recalled that the course dose of isotretinoin is the key to ensuring the duration of remission of the disease. In particular, according to AAD recommendations, relapses are less common at doses > 120 mg/kg than at doses < 120 mg/kg. The optimal dose for severe acne is 120–150 mg/kg. When using the drug at a dose of 220 mg / kg, the risk of relapse is even less. The likelihood of relapse is significantly increased at low doses, requiring a longer course of treatment5,6.
Professor E.R. Arabian, in turn, noted that the problem of using low doses is very important, since it is very tempting to lead a patient with a minimum risk of side effects, but it is important for the doctor to be aware of the risk of disease recurrence if the patient does not receive the recommended course dose.
A correctly calculated dose is not a guarantee of success, but the adherence of patients to the prescribed therapy and the correct intake of the drug are no less significant. When treating conventional isotretinoin drugs, it is important to take drugs with fatty foods, which help isotretinoin to be absorbed in the digestive tract. In particular, in an article on practical recommendations for doctors, to which E.R. Arabian referred at the beginning of her speech, emphasizing the need to check the patient’s intake of the drug along with food, if the doctor noted the insufficient effectiveness of isotretinoin treatment.
A.V. Samtsov drew the attention of the audience to the fact that, in this regard, the results of studies evaluating the effect of food intake on the absorption of isotretinoin created using LIDOSE technology are of particular interest. According to presented by Professor A.V. According to male data, the bioavailability of Acnecutane is much less dependent on its intake with food and is almost twice as high as the bioavailability of conventional isotretinoin (Fig. 5).
Thus, the LIDOSE system provides the necessary conditions for efficient and rapid absorption of the dose of the active substance declared in the capsule. This allows you to use the drug regardless of the meal.
Professor M.M. Kohan confirmed the high significance of the less dependence of absorption of Acnecutane on food for the treatment of patients, especially adolescents, for whom adherence to the rules of taking the drug for several months can be difficult. In addition, she drew attention to the fact that in order to ensure even greater adherence of patients to the prescribed therapy, the Yadran company developed the Aknekutan mobile application for patients and a virtual doctor’s office for doctors.
The Aknekutan application helps patients to comply with the rules for taking the drug, reminds them of the upcoming visit to the doctor and the delivery of tests. It can also save the results of blood tests, photographs of the patient at different stages of treatment, monitor the current course dose and the remaining time of therapy. All information entered by patients in the application is displayed in the virtual office of the attending physician. Thus, the doctor can monitor the effectiveness and tolerability of therapy in real time. In addition, through the doctor’s virtual office, the doctor also gets access to the latest scientific publications about Aknecutan.
Summarizing the above, Professor A.L. Bakulev noted that the key to successful acne therapy and the absence of relapses is compliance with the course dose of Aknekutan at 100–120 mg/kg.
The modern LIDOSE technology used in the production of Acnecutane reduces the risk of side effects and reduces the dependence of drug absorption on food intake.
The Aknekutan application and the virtual doctor’s office developed by Yadran make it possible to increase patients’ compliance with the prescribed therapy.