Information on cyclosporine as a treatment for psoriasis.

Ciclosporin is a medication administered orally and used for various types of diseases, including for the psoriasis. It has the ability to block certain cells that play a part in immune responses thus acting as an immunosuppressive drug that demonstrates an efficacy similar to that of the methotrexate.

What molecular mechanisms does cyclosporine employ to act on psoriasis?

Ciclosporin has the ability to inhibit the activation of T lymphocytes by reducing the levels of nuclear factors in T cells, thereby decreasing the production of inflammatory cytokines. Ciclosporin also has an effect on dendritic cells and in reducing the genes of the Th17 pathway, by lowering the levels of tumour necrosis factor (TNF), inducible nitric oxide synthase, as well as IL-23p19, IL-17 and IL-22. As a reminder, the Th17 pathway plays a direct role in the onset of psoriasis.

Ciclosporin treatment is administered orally in the form of 10, 25, 50, and 100 mg capsules. The treatment should be taken twice a day, once in the morning and once in the evening. The amount of ciclosporin to be taken depends on both the weight of the individual and the nature of the disease being treated.

Typically, the treatment begins with a dosage ranging from 2 mg/kg to 5 mg/kg per day. Studies have shown that cyclosporine at doses of 2.5 to 5 mg/kg per day over a period of 12 to 16 weeks results in a rapid and significant improvement of psoriasis in 80 to 90% of patients.

For psoriasis, the duration of treatment with ciclosporin can range from a few months to several years, depending on tolerance and effectiveness. Generally, it is recommended to limit continuous treatment to a maximum of two years.

The effectiveness of the treatment varies from one patient to another. As a general rule, a significant improvement in psoriasis is observed in 60 to 80% of patients. Maximum effectiveness is usually achieved after about 3 to 4 months of treatment and is maintained during the course of treatment in most cases. Often, the first positive signs of treatment become noticeable after a month. When treatment is stopped, skin lesions typically reappear between 2 and 4 months. However, the severity of the skin condition is generally less pronounced than before the start of treatment.

Some adverse effects have been reported following treatment with cyclosporine.

• Frequent adverse effects.

  Common adverse effects occur at the beginning of treatment. These may include fatigue, finger tremors, tingling sensations in the fingers or feet, headaches, and muscle pain. These effects are observed in 10 to 20% of patients. Digestive problems, such as nausea, abdominal pain, and diarrhoea, may also be observed at the start of treatment.

• Impairment of kidney function.

  An impairment of kidney function can occur during prolonged treatments with ciclosporin. If this were to happen, it would be necessary to reduce the dosage or discontinue the treatment. This adverse effect is reversible upon cessation of the treatment, hence the importance of close monitoring.

• Emergence of infections.

  Furthermore, cyclosporine can reduce the body's immune defences, thereby promoting the onset of infections. If you experience a fever during treatment, it is imperative to consult your doctor.

• May increase the risk of skin cancers in certain cases.

  In patients who have undergone numerous sessions of phototherapy (especially PUVA), the treatment can increase the risk of developing skin cancers. Therefore, it is essential to have regular monitoring by a dermatologist and to seek consultation in case of the appearance of new skin lesions.

It is crucial to avoid the use of certain medications, as incompatibilities can occur between some of them and cyclosporine. Some medications enhance the renal toxicity of cyclosporine, particularly non-steroidal anti-inflammatory drugs and aminoglycosides. It is important to inform your doctor that you are taking a cyclosporine-based treatment in order to check any new medication prescription to prevent interactions.

The treatment does not affect fertility, however, breastfeeding is not recommended. For pregnant women, ciclosporin can be used in cases of severe psoriasis that is resistant to narrow-band UVB phototherapy, as it does not cause foetal malformations. However, it may increase certain pregnancy complications, such as high blood pressure and prematurity. Therefore, the continuation or introduction of ciclosporin treatment during pregnancy requires close and specific monitoring, and the treatment should be reassessed on a case-by-case basis.

The use of ciclosporin is not recommended in patients suffering from chronic infections, such as Hepatitis C Virus (HCV) infection. Indeed, due to the strong immunosuppressive nature of ciclosporin, it makes patients more susceptible to bacterial, viral, and fungal infections.

In general, a regular follow-up with your doctor and dermatologist is necessary during the treatment.

• GROSSMAN R. M. & al. Long-term safety of Cyclosporine in the treatment of psoriasis. Archives of Dermatology (1996).

• ROSMARIN D. M. & al. Cyclosporine and psoriasis: 2008 National Psoriasis Foundation* Consensus Conference. The American Academy of Dermatology (2009).

• Lettre d’information pour le traitement du psoriasis par la ciclosporine orale. Groupe de recherche sur le psoriasis de la Société française de dermatologie. Annales de Dermatologie et de Vénéréologie (2011).

• Ciclosporine orale. Association France Psoriasis (2020).